NewbornGeneID > Associated Diseases

Frequently asked questions

USHER SYNDROME

Usher Syndrome Type 1B (MYO7A)


Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the MYO7A gene (Usher syndrome type 1B). MYO7A encodes for the protein myosin VIIA, which is involved in molecular transport. MYO7A is produced in the retina and inner ear, and is important for proper functioning. In the inner ear, it is involved in the production and maintenance of the hair-like stereocilia, which are essential for hearing. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. Usher syndrome type 1 affects overly 12,000 people in the USA alone. Roughly half of these are due to MYO7A mutations. Usher syndrome type 1 is more common in certain ethnic groups such as Ashkenazi Jews and the Acadians (Cajuns) of Louisiana. The condition is autosomal recessive, which typically requires both parents to be carriers, and usually are asymptomatic.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type 1,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1265/

NIH, Genetic Home Reference: MYO7A gene.

See http://ghr.nlm.nih.gov/gene/MYO7A

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract




Usher Syndrome Type 1F (PCDH15)


Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the PCDH15 gene (Usher syndrome type 1F). PCDH15 encodes for the protein protocadherin 15, which is produced in the retina and inner ear, and is involved with cell adhesion. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod receptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. The prevalence of Usher syndrome type 1 in the USA is over 4 in 100,000. Out of 34 families with Usher syndrome type 1, 6 were found to have defects in the PCDH15 gene. Usher syndrome type 1 is more common in certain ethnic groups, such as Ashkenazi Jews (where PCDH15 defects are believed to be particularly important) and the Acadians (Cajuns) of Louisiana. The condition is autosomal recessive, which typically requires an affected child to have two asymptomatic carrier parents.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type 1,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1265/

NIH, Genetic Home Reference: PCDH15 gene.

See http://ghr.nlm.nih.gov/gene/PCDH15

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract




Usher Syndrome Type 1C (USH1C)


Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the USH1C gene (Usher syndrome type 1C). USH1C encodes for the scaffold protein harmonin, which is produced in the retina and inner ear. It has a vital role in the stereocilia, the hair-like structures in the inner ear which are essential for stimulating neural pathways responsible for hearing. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. The prevalence of Usher syndrome type 1 in the USA is over 4 in 100,000. Out of 34 families with Usher syndrome type 1, only 2 were found to have defects in the USH1C gene. Usher syndrome type 1 is more common in certain ethnic groups, such as Ashkenazi Jews and the Acadians (Cajuns) of Louisiana. In the latter group, mutations of the USH1C gene are the main cause of the disease, although the gene is a minor cause for other populations. The condition is autosomal recessive, so typically an affected child will have two asymptomatic carrier parents.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type 1,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1265/

NIH, Genetic Home Reference: USH1C gene.

See http://ghr.nlm.nih.gov/gene/USH1C

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract




Usher Syndrome Type 2A (USH2A)


Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 2 are usually born with some hearing impairment: typically they cannot hear higher frequencies. Progressive vision loss occurs slowly from the teenage years onwards, although some vision may be retained for many decades. A number of different genetic mutations can cause Usher syndrome type 2, including those of the USH2A gene (Usher syndrome type 2A). USH2A encodes for the protein usherin, which forms basement membranes in the inner ear and retina. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (affecting day time vision as well). Unlike Usher syndrome type 1, Usher syndrome type 2 does not affect a child’s balance or their ability to stand up and walk. The prevalence of Usher syndrome type 2 in the USA is unknown, but it is believed to be more common than type 1, which occurs in over 4 in 100,000 people. The large number of relatively mild cases of type 2 mean that it is difficult to obtain accurate figures. It is estimated that 57-79% of Usher syndrome type 2 cases are caused by mutations in the USH2A gene. The condition is autosomal recessive, so typically an affected child will have two asymptomatic carrier parents.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type II,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1341/

NIH, Genetic Home Reference: USH2A gene.

See http://ghr.nlm.nih.gov/gene/USH2A

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome




Usher Syndrome Type 1D (CDH23)


Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the CDH23 gene (Usher syndrome type 1D). CDH23 encodes for the protein cadherin 23, which is involved in cell aggregation, including aggregation in the retina and ear. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. The prevalence of Usher syndrome type 1 in the USA is over 4 in 100,000. The number due to CDH23 mutations is relatively low. In a survey of 34 families with members affected by Usher syndrome type 1, only 6 were affected by defects in the CDH23 gene. Usher syndrome type 1 is more common in certain ethnic groups, such as Ashkenazi Jews and the Acadians (Cajuns) of Louisiana. The condition is autosomal recessive, so typically an affected child will have two asymptomatic carrier parents.

Sources

NIH, Genetic Home Reference: CDH23 gene.

See http://ghr.nlm.nih.gov/gene/CDH23

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract





Frequently asked questions

CYSTIC FIBROSIS AND CF-RELATED DISORDERS

Cystic Fibrosis (CFTR)


Cystic Fibrosis is caused by defects in the CFTR gene. The gene encodes for the protein cystic fibrosis transmembrane conductance regulator, which is involved in chloride ion transport and hence mucus production. Sufferers have breathing difficulties, due to sticky mucus buildup in the lungs. They also have severe digestive problems, since pancreatic enzymes are blocked from entering the small intestine, the main locus of nutrient absorption. Male sufferers are normally infertile, due to the lack of functioning vas deferens tubes which lead to the urethra. Diabetes and liver disease are common complications that often develop over time. The mean projected survival time for children born with the condition in the USA in 2010 was estimated at 37 years for women and 40 years for men. The inheritance of the defective gene is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the mutated gene. The condition is relatively common among Caucasian Americans, with an incidence of about 1 in 2,500 to 1 in 3,500. The figures are about 1 in 4,000 to 10,000 for Hispanic Americans, 1 in 15,000 to 20,000 for African Americans, and 1 in 100,000 for Asian Americans. It is estimated that 1 in 29 Caucasian Americans carry the defective gene asymptomatically. The figures are 1 in 46 for Hispanic Americans, 1 in 65 for African Americans, and 1 in 90 for Asian Americans.

Sources

Cystic Fibrosis Foundation, Carrier Testing for CF.

See http://www.cff.org/AboutCF/Testing/Genetics/GeneticCarrierTest/

MacKenzie, T. et al. (2014), “Longevity of Patients with Cystic Fibrosis in 2000 to 2010 and Beyond: Survival Analysis of the Cystic Fibrosis Foundation Patient Registry,”

Annals of Internal Medicine, 161, 233-241.

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis




Cystic Fibrosis (SCNN1A)


Cystic Fibrosis is caused by defects in the CFTR gene, however defects in the SCNN1A gene can give similar symptoms. The SCNN1A gene encodes for a subunit of the epithelial sodium channel protein. In some cases a mutation on the CFTR gene may act together with a mutation on the SCNN1A gene to give a cystic fibrosislike disease. Patients have breathing difficulties due to sticky mucus that builds up in the lungs. They may also have severe digestive problems since digestive enzymes from the pancreas are blocked by thick mucus. Male sufferers may be infertile, due to the lack of functioning vas deferens tubes which transfer sperm to the urethra. Diabetes and liver disease are common complications that often develop over time. However, some of the symptoms may be absent with non-typical cystic fibrosis. Non-typical cystic fibrosis from SCNN1A mutations is a rare disease, but may be underreported. No reliable estimates are available for its prevalence.

Sources

John Hopkins Website: CF and CF-Related Disorders.

See http://www.hopkinsmedicine.org/dnadiagnostic/CF_CFRelated_Panel.htm

Mutesa, L., et al. (2009), “Genetic analysis of Rwandan patients with cystic fibrosislike symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants,” Chest, 135, 1233-1242.

See http://journal.publications.chestnet.org/article.aspx?articleid=1089797

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis

NIH, Genetic Home Reference: SCNN1A gene. See http://ghr.nlm.nih.gov/gene/SCNN1A

Ramos, M.D. et al, (2014), “Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosislike phenotypes,” Clinical Genetics, 86, 91-95.

See http://onlinelibrary.wiley.com/doi/10.1111/cge.12234/references




Cystic Fibrosis (SCNN1B)


Cystic Fibrosis is caused by defects in the CFTR gene, however defects in the SCNN1B gene can give similar symptoms. The SCNN1B gene encodes for a subunit of the epithelial sodium-channel protein. In some cases a mutation on the CFTR gene may act together with a mutation on the SCNN1B gene to give a cystic fibrosislike disease. Sufferers have breathing difficulties, due to sticky mucus buildup in the lungs. They may also have severe digestive problems, since digestive enzymes from the pancreas are blocked from entering the small intestine, the main location of nutrient absorption. Male sufferers may be infertile, due to the lack of functioning vas deferens tubes which lead to the urethra. Diabetes and liver disease are common complications that often develop over time. However, some of the symptoms may be absent with non-typical cystic fibrosis. Non-typical cystic fibrosis from SCNN1B mutations is a rare disease, but may be underreported. No reliable estimates are available for its prevalence.

Sources

John Hopkins Website: CF and CF-Related Disorders.

See http://www.hopkinsmedicine.org/dnadiagnostic/CF_CFRelated_Panel.htm

Mutesa, L., et al. (2009), “Genetic analysis of Rwandan patients with cystic fibrosislike symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants,” Chest, 135, 1233-1242.

See http://journal.publications.chestnet.org/article.aspx?articleid=1089797

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis

NIH, Genetic Home Reference: SCNN1B gene.

See http://ghr.nlm.nih.gov/gene/SCNN1B

Ramos, M.D. et al, (2014), “Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosislike phenotypes,” Clinical Genetics, 86, 91-95.

See http://onlinelibrary.wiley.com/doi/10.1111/cge.12234/references




Cystic Fibrosis (CA12)


Cystic Fibrosis is caused by defects in the CFTR gene. However, defects in the CA12 gene can lead to individuals with high sweat chloride concentrations. Such high levels are normally indicative of cystic fibrosis, but in these cases the other symptoms of classical cystic fibrosis are not present: there is no evidence of lung disease or poor pancreatic function leading to digestive problems. Usually males with classical cystic fibrosis are sterile, but since the CA12 related condition has mainly been described in children, it’s not clear whether it’s normally associated with male sterility. The CA12 gene encodes for the carbonic anhydrase 12 enzyme. Children with the condition had low levels of sodium (hyponatremia), high levels of potassium (hyperkalemia), suffered from dehydration, and failed to thrive in the first year. Normal growth usually resumes after one year of age. Elevated sweat chloride levels from mutations in the CA12 gene is an extremely rare disease. Initial studies focused on a group of related Bedouin in Israel, but it is not known if the condition is more common in any particular ethnic group. The condition is autosomal recessive, which typically requires an affected child to have two asymptomatic carrier parents.

Sources

Feldshtein, M. et al. (2010), “Hyperchlorhidrosis Caused by Homozygous Mutation in CA12, Encoding Carbonic Anhydrase XII,” American Journal of Human Genetics, 87, 713-720.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978943/

John Hopkins Website: CF and CF-Related Disorders.

See http://www.hopkinsmedicine.org/dnadiagnostic/CF_CFRelated_Panel.htm

Muhammed, E. et al. (2011), “Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12,” Human Genetics,129, 397-405.

See http://link.springer.com/article/10.1007%2Fs00439-010-0930-4

NIH, Genetic Home Reference: CA12 gene.

See http://ghr.nlm.nih.gov/gene/CA12

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis





Frequently asked questions

LONG Q-T SYNDROME

Long QT Syndrome 5 (KCNE1)


Long QT Syndrome 5 (KCNE1) Long QT syndrome 5 (LQT5) is a heart condition caused by defects in the KCNE1 gene, which encodes for a protein involved in potassium channel regulation. Potassium channels in the heart muscles are important for maintaining a consistent heartbeat Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which may result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it is important that any fainting episodes are properly investigated. Treatments are by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome.

Overall, it’s estimated that about 1 in 2,000 people, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT5 (KCNE1 gene) only makes up <1% of the total cases of LQT, leading to less than 1 in 200,000 having the condition. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNE1 gene.

See http://ghr.nlm.nih.gov/gene/KCNE1

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome

Splawski, I. et al. (1997), “Mutations in the hminK gene cause long QT syndrome and suppress IKs function,” Nature Genetics, 17, 338-340.

See http://www.ncbi.nlm.nih.gov/pubmed/9354802




Long QT Syndrome 6 (KCNE2)


Long QT syndrome 6 (LQT6) is a heart condition caused by defects in the KCNE2 gene, which encodes for a protein involved in potassium channel regulation. Potassium channels in the heart muscles are important for maintaining a consistent heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndromes, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 150,000 people suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT6 (KCNE2 gene) only makes up <1% of the total cases of LQT, so less than 1 in 200,000, or 1,500 people, have the condition. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNE2 gene.

See http://ghr.nlm.nih.gov/gene/KCNE2

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome




Long QT Syndrome 1 (KCNQ1)


Long QT syndrome 1 (LQT1) is a heart condition caused by defects in the KCNQ1 gene, which encodes for a protein involved with potassium channels, which are fundamental for maintaining a consistent heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2,000 people suffer from LQT, translating to approximately 150,000 cases. The condition does not seem to be more prevalent in any ethnic group. LQT1 makes up 30 to 35% of the total cases of LQT, so roughly 1 in 6,000, or 50,000 cases, have the condition caused by the KCNQ1 gene. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNQ1 gene.

See http://ghr.nlm.nih.gov/gene/KCNQ1

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome




Long QT Syndrome 3 (SCN5A)


Long QT syndrome 3 (LQT3), is a heart condition caused by defects in the SCN5A gene, which encodes for a protein, sodium channel voltage gated type V alpha subunit, that makes up sodium channels. Such channels in the heart muscles are important for maintaining a regular heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2,000, or 150,000 people, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT3 makes up 5 to 10% of the total cases of LQT, roughly 1 in 20,000 to 1 in 40,000 have the condition caused by the SCN5A gene. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: SCN5A gene.

See http://ghr.nlm.nih.gov/gene/SCN5A

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome




Long QT Syndrome 11 (AKAP9)


Long QT syndrome 11 (LQT11) is a heart condition caused by defects in the “A kinase anchor protein 9,” or AKAP9 gene, which encodes for protein AKAP9. It is involved in the anchoring of the protein kinase A enzyme complex in the cell and other cellular functions. In the heart, protein kinase A is involved in the activation of various ion channel proteins through phosphorylation, which are important for maintaining a regular heartbeat. Long QT refers to the abnormal signal on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which may result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it is important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2000 people, or 150,000 cases, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

Chen, L. et al. (2007), “Mutation of an A-kinase-anchoring protein causes long-QT syndrome,” Proc. Acad. Natl. Sci. U.S.A.,” 104, 20990 – 20995.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409254/

NIH, Genetics Home Reference: AKAP9 gene.

See http://ghr.nlm.nih.gov/gene/AKAP9

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome





Frequently asked questions

USHER SYNDROME

Usher Syndrome Type 1B (MYO7A)


Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the MYO7A gene (Usher syndrome type 1B). MYO7A encodes for the protein myosin VIIA, which is involved in molecular transport. MYO7A is produced in the retina and inner ear, and is important for proper functioning. In the inner ear, it is involved in the production and maintenance of the hair-like stereocilia, which are essential for hearing. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. Usher syndrome type 1 affects overly 12,000 people in the USA alone. Roughly half of these are due to MYO7A mutations. Usher syndrome type 1 is more common in certain ethnic groups such as Ashkenazi Jews and the Acadians (Cajuns) of Louisiana. The condition is autosomal recessive, which typically requires both parents to be carriers, and usually are asymptomatic.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type 1,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1265/

NIH, Genetic Home Reference: MYO7A gene.

See http://ghr.nlm.nih.gov/gene/MYO7A

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract




Usher Syndrome Type 1F (PCDH15)


Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the PCDH15 gene (Usher syndrome type 1F). PCDH15 encodes for the protein protocadherin 15, which is produced in the retina and inner ear, and is involved with cell adhesion. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod receptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. The prevalence of Usher syndrome type 1 in the USA is over 4 in 100,000. Out of 34 families with Usher syndrome type 1, 6 were found to have defects in the PCDH15 gene. Usher syndrome type 1 is more common in certain ethnic groups, such as Ashkenazi Jews (where PCDH15 defects are believed to be particularly important) and the Acadians (Cajuns) of Louisiana. The condition is autosomal recessive, which typically requires an affected child to have two asymptomatic carrier parents.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type 1,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1265/

NIH, Genetic Home Reference: PCDH15 gene.

See http://ghr.nlm.nih.gov/gene/PCDH15

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract




Usher Syndrome Type 1C (USH1C)


Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the USH1C gene (Usher syndrome type 1C). USH1C encodes for the scaffold protein harmonin, which is produced in the retina and inner ear. It has a vital role in the stereocilia, the hair-like structures in the inner ear which are essential for stimulating neural pathways responsible for hearing. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. The prevalence of Usher syndrome type 1 in the USA is over 4 in 100,000. Out of 34 families with Usher syndrome type 1, only 2 were found to have defects in the USH1C gene. Usher syndrome type 1 is more common in certain ethnic groups, such as Ashkenazi Jews and the Acadians (Cajuns) of Louisiana. In the latter group, mutations of the USH1C gene are the main cause of the disease, although the gene is a minor cause for other populations. The condition is autosomal recessive, so typically an affected child will have two asymptomatic carrier parents.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type 1,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1265/

NIH, Genetic Home Reference: USH1C gene.

See http://ghr.nlm.nih.gov/gene/USH1C

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract




Usher Syndrome Type 2A (USH2A)


Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 2 are usually born with some hearing impairment: typically they cannot hear higher frequencies. Progressive vision loss occurs slowly from the teenage years onwards, although some vision may be retained for many decades. A number of different genetic mutations can cause Usher syndrome type 2, including those of the USH2A gene (Usher syndrome type 2A). USH2A encodes for the protein usherin, which forms basement membranes in the inner ear and retina. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (affecting day time vision as well). Unlike Usher syndrome type 1, Usher syndrome type 2 does not affect a child’s balance or their ability to stand up and walk. The prevalence of Usher syndrome type 2 in the USA is unknown, but it is believed to be more common than type 1, which occurs in over 4 in 100,000 people. The large number of relatively mild cases of type 2 mean that it is difficult to obtain accurate figures. It is estimated that 57-79% of Usher syndrome type 2 cases are caused by mutations in the USH2A gene. The condition is autosomal recessive, so typically an affected child will have two asymptomatic carrier parents.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type II,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1341/

NIH, Genetic Home Reference: USH2A gene.

See http://ghr.nlm.nih.gov/gene/USH2A

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome




Usher Syndrome Type 1D (CDH23)


Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the CDH23 gene (Usher syndrome type 1D). CDH23 encodes for the protein cadherin 23, which is involved in cell aggregation, including aggregation in the retina and ear. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. The prevalence of Usher syndrome type 1 in the USA is over 4 in 100,000. The number due to CDH23 mutations is relatively low. In a survey of 34 families with members affected by Usher syndrome type 1, only 6 were affected by defects in the CDH23 gene. Usher syndrome type 1 is more common in certain ethnic groups, such as Ashkenazi Jews and the Acadians (Cajuns) of Louisiana. The condition is autosomal recessive, so typically an affected child will have two asymptomatic carrier parents.

Sources

NIH, Genetic Home Reference: CDH23 gene.

See http://ghr.nlm.nih.gov/gene/CDH23

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract





Frequently asked questions

SPINAL MUSCULAR ATROPHY

Spinal Muscular Atrophy (SMN1 Linked) (Werdnig-Hoffman)


Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes. One of these is the SMN1 gene, which encodes for the spinal motor neuron protein. This protein is required for the maintenance of motor neurons in the spinal cord and brainstem. SMA is divided into different types: types 1-4 of SMA are all caused by mutations of the SMN1 gene, and all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up; they typically have difficulty swallowing and breathing, so they tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of all types of spinal muscular atrophy is around 1 in 6,000 to 1 in 10,000 births. It is estimated that around 1 in 40 to 1 in 50 people is a carrier. Although the incidence varies somewhat from country to country, it does not seem to be highly present in any ethnic group. The faulty gene is transmitted in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

NIH, Genetics Home Reference: SMN1 gene.

See http://ghr.nlm.nih.gov/gene/SMN1

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

Prior, T.W. & Russman, B.S., (2000), “Spinal Muscular Atrophy,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1352/

Recombine Website. Spinal Muscular Atrophy: SMN1 linked.

See https://recombine.com/diseases/spinal-muscular-atrophy-smn1-linked




Modification of the Severity of Spinal Muscular Atrophy (SMN2)


Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes. One of these is the SMN1 gene, which encodes for the spinal motor neuron protein. This protein is required for the maintenance of motor neurons in the spinal cord and brainstem. The SMN2 gene is also capable, to some extent, of producing spinal neuron protein. Most people have two or fewer copies of the SMN2 gene. However, some have three or more copies. In this latter group, the extra copies of the SMN2 gene can moderate the effects of mutations in the SMN1 gene, making any resulting SMA disease less severe than it would otherwise have been. SMA is divided into different types: types 1-4 of SMA are all caused by mutations of the SMN1 gene, and all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, and tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. It has been shown that patients from type 3 SMA are much more likely to have 3 or more copies of the SMN2 gene than patients from type 1 or the general population. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of all types of spinal muscular atrophy is around 1 in 6,000 to 1 in 10,000 births. It is estimated that around 1 in 40 to 1 in 50 people is a carrier. Although the incidence varies somewhat from country to country, it does not seem to be highly present in any ethnic group. The faulty SMN1 gene is transmitted in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

Mailman, M.D. et al. (2002), “”Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2,” Genetics in Medicine, 4, 20-26.

See http://www.nature.com/gim/journal/v4/n1/full/gim20024a.html

NIH, Genetics Home Reference: SMN1 gene.

See http://ghr.nlm.nih.gov/gene/SMN1

NIH, Genetics Home Reference: SMN1 gene.

See http://ghr.nlm.nih.gov/gene/SMN2

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

Prior, T.W. & Russman, B.S., (2000), “Spinal Muscular Atrophy,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1352/

Recombine Website. Spinal Muscular Atrophy: SMN1 linked.

See https://recombine.com/diseases/spinal-muscular-atrophy-smn1-linked




Spinal Muscular Atrophy (UBA1)


Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes, most commonly the SMN1 gene. However, it can also be caused by the UBA1 gene, which encodes for the ubiquitin-activating enzyme E1. SMA from UBA1 is referred to as X-linked SMA, as the gene resides on the X chromosome. This ubiquitin-activating enzyme breaks down unwanted proteins which can damage motor neurons responsible for muscle movement. Babies usually exhibit muscle weakness from birth, and are prone to lung disease and bone fractures. Typically, breathing becomes progressively more difficult, and very few survive childhood. Other types of SMA are the result of SMN1 mutations. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, so tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of spinal muscular atrophy (all types) is around 1 in 6,000 to 1 in 10,000 births. However, SMA caused by the UBA1 gene is very rare. Less than 20 families with this condition have been found by researchers. The gene is on the Xchromosome, which affects males far more than females, as males only have one Xchromosome, and are affected by the disease if the chromosome carries a mutated UBA1 gene. For females, both X-chromosomes need to have a mutated UBA1 gene for the disease to occur, which is very unlikely. A woman with a mutated UBA1 gene on one X-chromosome can act as a carrier without showing symptoms.

Sources

Baumbach-Reardon, L. et al. (2008), “Spinal Muscular Atrophy, X-Labelled Infantile,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK2594/

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

NIH, Genetics Home Reference: UBA1 gene.

See http://ghr.nlm.nih.gov/gene/UBA1




Spinal Muscular Atrophy (VAPB)


Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes, usually the SMN1 gene. However, a few cases of adult-onset SMA have been linked to mutations in the VAPB gene, which produces the protein named “VAMP-associated protein B and C.” Those with SMA from VAPB mutations begin to suffer from progressive muscle weakness, and may have cramps, tremors, and swallowing or breathing difficulties. Symptoms can begin at any age between 20 and 60. SMA from SMN1 defects is divided into different types, types 1-4: all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, so tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of spinal muscular atrophy (all types) is around 1 in 6,000 to 1 in 10,000 births. However, the adult-onset form related to the VAPB gene is much rarer, having only been found in a small number of families. The faulty gene is transmitted in an autosomal dominant manner, typically requiring at least one affected parent. If an asymptomatic parent died at a relatively young age, it is possible that the disease did not have time to present itself. The faulty gene is also associated with some cases of ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig’s disease.

Sources

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

NIH, Genetics Home Reference: VAPB gene.

See http://ghr.nlm.nih.gov/gene/VAPB

Nishimura, A.L. et al. (2004), “A Mutation in the Vesicle-Trafficking Protein VAPB Causes Late-Onset Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis,” American Journal of Human Genetics, 75, 822-831.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182111/

Richieri-Costa, A. et al. (1981), “Autosomal dominant late adult spinal muscular atrophy, type Finkel,” American Journal of Medical Genetics, 9, 119-128.

See http://www.ncbi.nlm.nih.gov/pubmed/7258225




Spinal Muscular Atrophy (DYNC1H1)


Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes, usually the SMN1 gene. However, in a few cases SMA is caused by mutations in the DYNC1H1 gene. This gene encodes for a protein that is part of a motor protein complex called dynein. If dynein is ineffective in moving proteins and other materials around cells, the motor neurons in the spinal cord may not function properly. The SMA caused by the DYNC1H1 gene causes muscle weakness only in the lower limbs, particularly the thigh muscles, so is referred to as spinal muscular atrophy, lower extremity, dominant (SMA-LED). Sufferers find it difficult to climb stairs, get up from a chair, or walk long distances. The disease normally first occurs in childhood, but is not life-threatening. SMA caused by SMN1 defects is divided into different types; types 1-4 of SMA all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, and tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of spinal muscular atrophy (all types) is around 1 in 6,000 to 1 in 10,000 births. However, SMA from DYNC1H1 mutations only affects a small number of families. Unlike SMN1 defects, which are autosomal recessive, the mutations in DYNC1H1 are autosomal dominant. Typically, autosomal dominant inheritance require at least one affected parent.

Sources

NIH, Genetics Home Reference: DYNC1H1 gene.

See http://ghr.nlm.nih.gov/gene/DYNC1H1

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

Harms, M.B. et al. (2010), “Dominant spinal muscle atrophy with lower extremity predominance,” Neurology, 75, 539-546.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918478/





Frequently asked questions

LONG Q-T SYNDROME

Long QT Syndrome 5 (KCNE1)


Long QT Syndrome 5 (KCNE1) Long QT syndrome 5 (LQT5) is a heart condition caused by defects in the KCNE1 gene, which encodes for a protein involved in potassium channel regulation. Potassium channels in the heart muscles are important for maintaining a consistent heartbeat Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which may result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it is important that any fainting episodes are properly investigated. Treatments are by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome.

Overall, it’s estimated that about 1 in 2,000 people, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT5 (KCNE1 gene) only makes up <1% of the total cases of LQT, leading to less than 1 in 200,000 having the condition. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNE1 gene.

See http://ghr.nlm.nih.gov/gene/KCNE1

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome

Splawski, I. et al. (1997), “Mutations in the hminK gene cause long QT syndrome and suppress IKs function,” Nature Genetics, 17, 338-340.

See http://www.ncbi.nlm.nih.gov/pubmed/9354802




Long QT Syndrome 6 (KCNE2)


Long QT syndrome 6 (LQT6) is a heart condition caused by defects in the KCNE2 gene, which encodes for a protein involved in potassium channel regulation. Potassium channels in the heart muscles are important for maintaining a consistent heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndromes, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 150,000 people suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT6 (KCNE2 gene) only makes up <1% of the total cases of LQT, so less than 1 in 200,000, or 1,500 people, have the condition. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNE2 gene.

See http://ghr.nlm.nih.gov/gene/KCNE2

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome




Long QT Syndrome 1 (KCNQ1)


Long QT syndrome 1 (LQT1) is a heart condition caused by defects in the KCNQ1 gene, which encodes for a protein involved with potassium channels, which are fundamental for maintaining a consistent heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2,000 people suffer from LQT, translating to approximately 150,000 cases. The condition does not seem to be more prevalent in any ethnic group. LQT1 makes up 30 to 35% of the total cases of LQT, so roughly 1 in 6,000, or 50,000 cases, have the condition caused by the KCNQ1 gene. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNQ1 gene.

See http://ghr.nlm.nih.gov/gene/KCNQ1

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome




Long QT Syndrome 3 (SCN5A)


Long QT syndrome 3 (LQT3), is a heart condition caused by defects in the SCN5A gene, which encodes for a protein, sodium channel voltage gated type V alpha subunit, that makes up sodium channels. Such channels in the heart muscles are important for maintaining a regular heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2,000, or 150,000 people, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT3 makes up 5 to 10% of the total cases of LQT, roughly 1 in 20,000 to 1 in 40,000 have the condition caused by the SCN5A gene. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: SCN5A gene.

See http://ghr.nlm.nih.gov/gene/SCN5A

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome




Long QT Syndrome 11 (AKAP9)


Long QT syndrome 11 (LQT11) is a heart condition caused by defects in the “A kinase anchor protein 9,” or AKAP9 gene, which encodes for protein AKAP9. It is involved in the anchoring of the protein kinase A enzyme complex in the cell and other cellular functions. In the heart, protein kinase A is involved in the activation of various ion channel proteins through phosphorylation, which are important for maintaining a regular heartbeat. Long QT refers to the abnormal signal on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which may result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it is important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2000 people, or 150,000 cases, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

Chen, L. et al. (2007), “Mutation of an A-kinase-anchoring protein causes long-QT syndrome,” Proc. Acad. Natl. Sci. U.S.A.,” 104, 20990 – 20995.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409254/

NIH, Genetics Home Reference: AKAP9 gene.

See http://ghr.nlm.nih.gov/gene/AKAP9

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome





Frequently asked questions

CYSTIC FIBROSIS AND CF-RELATED DISORDERS

Cystic Fibrosis (CFTR)


Cystic Fibrosis is caused by defects in the CFTR gene. The gene encodes for the protein cystic fibrosis transmembrane conductance regulator, which is involved in chloride ion transport and hence mucus production. Sufferers have breathing difficulties, due to sticky mucus buildup in the lungs. They also have severe digestive problems, since pancreatic enzymes are blocked from entering the small intestine, the main locus of nutrient absorption. Male sufferers are normally infertile, due to the lack of functioning vas deferens tubes which lead to the urethra. Diabetes and liver disease are common complications that often develop over time. The mean projected survival time for children born with the condition in the USA in 2010 was estimated at 37 years for women and 40 years for men. The inheritance of the defective gene is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the mutated gene. The condition is relatively common among Caucasian Americans, with an incidence of about 1 in 2,500 to 1 in 3,500. The figures are about 1 in 4,000 to 10,000 for Hispanic Americans, 1 in 15,000 to 20,000 for African Americans, and 1 in 100,000 for Asian Americans. It is estimated that 1 in 29 Caucasian Americans carry the defective gene asymptomatically. The figures are 1 in 46 for Hispanic Americans, 1 in 65 for African Americans, and 1 in 90 for Asian Americans.

Sources

Cystic Fibrosis Foundation, Carrier Testing for CF.

See http://www.cff.org/AboutCF/Testing/Genetics/GeneticCarrierTest/

MacKenzie, T. et al. (2014), “Longevity of Patients with Cystic Fibrosis in 2000 to 2010 and Beyond: Survival Analysis of the Cystic Fibrosis Foundation Patient Registry,”

Annals of Internal Medicine, 161, 233-241.

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis




Cystic Fibrosis (SCNN1A)


Cystic Fibrosis is caused by defects in the CFTR gene, however defects in the SCNN1A gene can give similar symptoms. The SCNN1A gene encodes for a subunit of the epithelial sodium channel protein. In some cases a mutation on the CFTR gene may act together with a mutation on the SCNN1A gene to give a cystic fibrosislike disease. Patients have breathing difficulties due to sticky mucus that builds up in the lungs. They may also have severe digestive problems since digestive enzymes from the pancreas are blocked by thick mucus. Male sufferers may be infertile, due to the lack of functioning vas deferens tubes which transfer sperm to the urethra. Diabetes and liver disease are common complications that often develop over time. However, some of the symptoms may be absent with non-typical cystic fibrosis. Non-typical cystic fibrosis from SCNN1A mutations is a rare disease, but may be underreported. No reliable estimates are available for its prevalence.

Sources

John Hopkins Website: CF and CF-Related Disorders.

See http://www.hopkinsmedicine.org/dnadiagnostic/CF_CFRelated_Panel.htm

Mutesa, L., et al. (2009), “Genetic analysis of Rwandan patients with cystic fibrosislike symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants,” Chest, 135, 1233-1242.

See http://journal.publications.chestnet.org/article.aspx?articleid=1089797

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis

NIH, Genetic Home Reference: SCNN1A gene. See http://ghr.nlm.nih.gov/gene/SCNN1A

Ramos, M.D. et al, (2014), “Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosislike phenotypes,” Clinical Genetics, 86, 91-95.

See http://onlinelibrary.wiley.com/doi/10.1111/cge.12234/references




Cystic Fibrosis (SCNN1B)


Cystic Fibrosis is caused by defects in the CFTR gene, however defects in the SCNN1B gene can give similar symptoms. The SCNN1B gene encodes for a subunit of the epithelial sodium-channel protein. In some cases a mutation on the CFTR gene may act together with a mutation on the SCNN1B gene to give a cystic fibrosislike disease. Sufferers have breathing difficulties, due to sticky mucus buildup in the lungs. They may also have severe digestive problems, since digestive enzymes from the pancreas are blocked from entering the small intestine, the main location of nutrient absorption. Male sufferers may be infertile, due to the lack of functioning vas deferens tubes which lead to the urethra. Diabetes and liver disease are common complications that often develop over time. However, some of the symptoms may be absent with non-typical cystic fibrosis. Non-typical cystic fibrosis from SCNN1B mutations is a rare disease, but may be underreported. No reliable estimates are available for its prevalence.

Sources

John Hopkins Website: CF and CF-Related Disorders.

See http://www.hopkinsmedicine.org/dnadiagnostic/CF_CFRelated_Panel.htm

Mutesa, L., et al. (2009), “Genetic analysis of Rwandan patients with cystic fibrosislike symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants,” Chest, 135, 1233-1242.

See http://journal.publications.chestnet.org/article.aspx?articleid=1089797

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis

NIH, Genetic Home Reference: SCNN1B gene.

See http://ghr.nlm.nih.gov/gene/SCNN1B

Ramos, M.D. et al, (2014), “Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosislike phenotypes,” Clinical Genetics, 86, 91-95.

See http://onlinelibrary.wiley.com/doi/10.1111/cge.12234/references




Cystic Fibrosis (CA12)


Cystic Fibrosis is caused by defects in the CFTR gene. However, defects in the CA12 gene can lead to individuals with high sweat chloride concentrations. Such high levels are normally indicative of cystic fibrosis, but in these cases the other symptoms of classical cystic fibrosis are not present: there is no evidence of lung disease or poor pancreatic function leading to digestive problems. Usually males with classical cystic fibrosis are sterile, but since the CA12 related condition has mainly been described in children, it’s not clear whether it’s normally associated with male sterility. The CA12 gene encodes for the carbonic anhydrase 12 enzyme. Children with the condition had low levels of sodium (hyponatremia), high levels of potassium (hyperkalemia), suffered from dehydration, and failed to thrive in the first year. Normal growth usually resumes after one year of age. Elevated sweat chloride levels from mutations in the CA12 gene is an extremely rare disease. Initial studies focused on a group of related Bedouin in Israel, but it is not known if the condition is more common in any particular ethnic group. The condition is autosomal recessive, which typically requires an affected child to have two asymptomatic carrier parents.

Sources

Feldshtein, M. et al. (2010), “Hyperchlorhidrosis Caused by Homozygous Mutation in CA12, Encoding Carbonic Anhydrase XII,” American Journal of Human Genetics, 87, 713-720.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978943/

John Hopkins Website: CF and CF-Related Disorders.

See http://www.hopkinsmedicine.org/dnadiagnostic/CF_CFRelated_Panel.htm

Muhammed, E. et al. (2011), “Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12,” Human Genetics,129, 397-405.

See http://link.springer.com/article/10.1007%2Fs00439-010-0930-4

NIH, Genetic Home Reference: CA12 gene.

See http://ghr.nlm.nih.gov/gene/CA12

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis





Frequently asked questions

LONG Q-T SYNDROME

Long QT Syndrome 5 (KCNE1)


Long QT Syndrome 5 (KCNE1) Long QT syndrome 5 (LQT5) is a heart condition caused by defects in the KCNE1 gene, which encodes for a protein involved in potassium channel regulation. Potassium channels in the heart muscles are important for maintaining a consistent heartbeat Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which may result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it is important that any fainting episodes are properly investigated. Treatments are by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome.

Overall, it’s estimated that about 1 in 2,000 people, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT5 (KCNE1 gene) only makes up <1% of the total cases of LQT, leading to less than 1 in 200,000 having the condition. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNE1 gene.

See http://ghr.nlm.nih.gov/gene/KCNE1

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome

Splawski, I. et al. (1997), “Mutations in the hminK gene cause long QT syndrome and suppress IKs function,” Nature Genetics, 17, 338-340.

See http://www.ncbi.nlm.nih.gov/pubmed/9354802




Long QT Syndrome 6 (KCNE2)


Long QT syndrome 6 (LQT6) is a heart condition caused by defects in the KCNE2 gene, which encodes for a protein involved in potassium channel regulation. Potassium channels in the heart muscles are important for maintaining a consistent heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndromes, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 150,000 people suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT6 (KCNE2 gene) only makes up <1% of the total cases of LQT, so less than 1 in 200,000, or 1,500 people, have the condition. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNE2 gene.

See http://ghr.nlm.nih.gov/gene/KCNE2

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome




Long QT Syndrome 1 (KCNQ1)


Long QT syndrome 1 (LQT1) is a heart condition caused by defects in the KCNQ1 gene, which encodes for a protein involved with potassium channels, which are fundamental for maintaining a consistent heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2,000 people suffer from LQT, translating to approximately 150,000 cases. The condition does not seem to be more prevalent in any ethnic group. LQT1 makes up 30 to 35% of the total cases of LQT, so roughly 1 in 6,000, or 50,000 cases, have the condition caused by the KCNQ1 gene. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNQ1 gene.

See http://ghr.nlm.nih.gov/gene/KCNQ1

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome




Long QT Syndrome 3 (SCN5A)


Long QT syndrome 3 (LQT3), is a heart condition caused by defects in the SCN5A gene, which encodes for a protein, sodium channel voltage gated type V alpha subunit, that makes up sodium channels. Such channels in the heart muscles are important for maintaining a regular heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2,000, or 150,000 people, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT3 makes up 5 to 10% of the total cases of LQT, roughly 1 in 20,000 to 1 in 40,000 have the condition caused by the SCN5A gene. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: SCN5A gene.

See http://ghr.nlm.nih.gov/gene/SCN5A

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome




Long QT Syndrome 11 (AKAP9)


Long QT syndrome 11 (LQT11) is a heart condition caused by defects in the “A kinase anchor protein 9,” or AKAP9 gene, which encodes for protein AKAP9. It is involved in the anchoring of the protein kinase A enzyme complex in the cell and other cellular functions. In the heart, protein kinase A is involved in the activation of various ion channel proteins through phosphorylation, which are important for maintaining a regular heartbeat. Long QT refers to the abnormal signal on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which may result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it is important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2000 people, or 150,000 cases, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

Chen, L. et al. (2007), “Mutation of an A-kinase-anchoring protein causes long-QT syndrome,” Proc. Acad. Natl. Sci. U.S.A.,” 104, 20990 – 20995.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409254/

NIH, Genetics Home Reference: AKAP9 gene.

See http://ghr.nlm.nih.gov/gene/AKAP9

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome





Frequently asked questions

NON-SYNDROMIC HEARING LOSS

Nonsyndromic Hearing Loss & Deafness (COL11A2)


Non-syndromic hearing loss can be caused by mutations in a number of genes, including the COL11A2 gene (referred to as DFNA13 hearing loss). This gene encodes for part of Type XI collagen. Type XI collagen plays a vital role in the inner ear, thus mutations in COL11A2 can lead to poor hearing, as the collagen fibrils in the ear lack their normal structure. Patients with this non-progressive deficiency find it particularly difficult to hear mid-level frequencies, while retaining the ability to detect low and high frequencies. Initial studies focused on two families, one in the USA and one in the Netherlands. It is not yet possible to determine the prevalence of hearing loss due to COL11A2, although it seems to be rare. It is not clear whether any ethnic group is particularly affected. The condition is autosomal dominant which normally is inherited from at least one affected parent.

Sources

McGuirt, W.T. et al. (1999), “Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13),” Nature Genetics, 23, 413-419.

See http://www.ncbi.nlm.nih.gov/pubmed/10581026

NIH, Genetic Home Reference: COL11A2 gene.

See http://ghr.nlm.nih.gov/gene/COL11A2

NIH, Genetics Home Reference: Nonsyndromic deafness.

See http://ghr.nlm.nih.gov/condition/nonsyndromic-deafness




Non-syndromic Hearing Loss and Deafness (GJB2) related (connexin 26) nonsyndromic deafness


Non-syndromic hearing loss can be caused by mutations in a number of genes, including the GJB2 gene, which causes what is known as DFNB1 deafness. The GJB2 gene encodes for a protein called connexin 26 (also known as gap junction beta 2), which is involved in producing gap junctions for the transport of ions, nutrients, and other important functions. Faulty connexin 26 in the inner ear can lead to hearing loss or deafness. The degree of hearing loss can vary widely between affected individuals. The disease is not progressive. The faulty GBJ2 gene is autosomal recessive, which typically requires both parents to be carriers of the faulty gene, usually occurring asymptomatically. DFNB1 deafness (i.e. deafness from the GJB2 gene, in around 98% of cases) is estimated to affect around 42,000 people in the USA/ Western Europe. Some ethnic groups, such as Palestinians, Iran Kurds, and Siberian Altaians have particularly high levels of the faulty gene.

Sources

NIH, Genetic Home Reference: GJB2 gene.

See http://ghr.nlm.nih.gov/gene/GJB2

NIH, Genetics Home Reference: Nonsyndromic deafness.

See http://ghr.nlm.nih.gov/condition/nonsyndromic-deafness

Smith, R.J.H. & Van Camp, G. (1998), “Nonsyndromic hearing loss and deafness: DFNB1,” in Pagon, R.A. et al., editors, GeneReview [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1272/




Non-syndromic Deafness (GJB3) (Connexin 31)


Non-syndromic hearing loss can be caused by mutations in a number of genes, including the GJB3 gene, which causes what is known as DFNA2B deafness. The GJB3 gene encodes for a protein called connexin 31 (also known as gap junction beta 3), which is involved in producing gap junctions for the transport of ions, nutrients, etc. Faulty connexin 31 in the inner ear can lead to hearing loss or deafness. Hearing loss is particularly marked in the higher frequencies. No reliable data on prevalence are available. The genetic defect and associated hearing loss were found in two Chinese families. There have been no subsequent reports on any such association, suggesting that it may be very rare. The faulty gene is autosomal dominant, which typically requires at least one affected parent.

Sources

NIH, Genetic Home Reference: GJB3 gene.

See http://ghr.nlm.nih.gov/gene/GJB3

NIH, Genetics Home Reference: Nonsyndromic deafness.

See http://ghr.nlm.nih.gov/condition/nonsyndromic-deafness

Smith, R.J.H. & Hilderbrand, M. (2008), “DFNA2 nonsyndromic hearing loss,” in Pagon, R.A. et al., editors, GeneReview [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1209/

Xia, J.H. et al. (1998), “Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment.” Nature Genetics, 20, 370- 373.

See https://www.ncbi.nlm.nih.gov/pubmed/9843210




Non-syndromic Deafness (KCNQ4)


Non-syndromic hearing loss can be caused by mutations in a number of genes, including the KCNQ4 gene, which causes what is known as DFNA2 deafness. The KCNQ4 gene encodes for a protein called potassium voltage-gated channel KQTlike protein 4, which is involved in potassium ion channel formation, particularly in the inner ear and auditory nerve. Hearing is particularly poor for high frequencies, but better for lower frequencies. The condition is progressive, and most patients will have to start wearing a hearing aid between the ages of 10 and 40. No reliable data on prevalence are available. There is no evidence that mutations in KCNQ4 are prevalent in any one ethnic group. The condition is autosomal dominant, which typically requires at least one affected parent.

Sources

NIH, Genetic Home Reference: KCNQ4 gene.

See http://ghr.nlm.nih.gov/gene/KCNQ4

NIH, Genetics Home Reference: Nonsyndromic deafness.

See http://ghr.nlm.nih.gov/condition/nonsyndromic-deafness

Smith, R.J.H. & Hilderbrand, M. (2008), “DFNA2 nonsyndromic hearing loss,” in Pagon, R.A. et al., editors, GeneReview [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1209/




Pendred syndrome (SLC26A4)


Pendred syndrome is a syndromic condition that involves deafness and the formation of a goiter on the thyroid gland. The gene SLC26A4 encodes a protein called pendrin, which is involved in anion transport. It is found in the thyroid (where it is believed to be involved in iodide ion transport), kidney, and inner ear. Those born with Pendred syndrome are normally deaf at birth, although in some cases deafness arrives during early childhood. A goiter is normally seen during adolescence or early adulthood. In some cases SLC26A4 defects cause deafness without any other symptoms, known as non-syndromic hearing loss, or DFNB4 deafness. The exact occurrence of Pendred syndrome is not known, although one estimate calculated that 7.5% of all congenital deafness are due to the syndrome. It is not clear whether some ethnic groups are more affected than others. The condition is autosomal recessive, which typically occurs when both parents of an affected child are asymptomatic carriers.

Sources

Alasti, F. et al. (1998), “Pendred Syndrome / DFNB4”. In Payon R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1467/

NIH, Genetic Home Reference: SLC26A4 gene.

See http://ghr.nlm.nih.gov/gene/SLC26A4

NIH, Genetics Home Reference: Pendred syndrome.

See http://ghr.nlm.nih.gov/condition/pendred-syndrome





Frequently asked questions

SPINAL MUSCULAR ATROPHY

Spinal Muscular Atrophy (SMN1 Linked) (Werdnig-Hoffman)


Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes. One of these is the SMN1 gene, which encodes for the spinal motor neuron protein. This protein is required for the maintenance of motor neurons in the spinal cord and brainstem. SMA is divided into different types: types 1-4 of SMA are all caused by mutations of the SMN1 gene, and all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up; they typically have difficulty swallowing and breathing, so they tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of all types of spinal muscular atrophy is around 1 in 6,000 to 1 in 10,000 births. It is estimated that around 1 in 40 to 1 in 50 people is a carrier. Although the incidence varies somewhat from country to country, it does not seem to be highly present in any ethnic group. The faulty gene is transmitted in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

NIH, Genetics Home Reference: SMN1 gene.

See http://ghr.nlm.nih.gov/gene/SMN1

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

Prior, T.W. & Russman, B.S., (2000), “Spinal Muscular Atrophy,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1352/

Recombine Website. Spinal Muscular Atrophy: SMN1 linked.

See https://recombine.com/diseases/spinal-muscular-atrophy-smn1-linked




Modification of the Severity of Spinal Muscular Atrophy (SMN2)


Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes. One of these is the SMN1 gene, which encodes for the spinal motor neuron protein. This protein is required for the maintenance of motor neurons in the spinal cord and brainstem. The SMN2 gene is also capable, to some extent, of producing spinal neuron protein. Most people have two or fewer copies of the SMN2 gene. However, some have three or more copies. In this latter group, the extra copies of the SMN2 gene can moderate the effects of mutations in the SMN1 gene, making any resulting SMA disease less severe than it would otherwise have been. SMA is divided into different types: types 1-4 of SMA are all caused by mutations of the SMN1 gene, and all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, and tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. It has been shown that patients from type 3 SMA are much more likely to have 3 or more copies of the SMN2 gene than patients from type 1 or the general population. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of all types of spinal muscular atrophy is around 1 in 6,000 to 1 in 10,000 births. It is estimated that around 1 in 40 to 1 in 50 people is a carrier. Although the incidence varies somewhat from country to country, it does not seem to be highly present in any ethnic group. The faulty SMN1 gene is transmitted in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

Mailman, M.D. et al. (2002), “”Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2,” Genetics in Medicine, 4, 20-26.

See http://www.nature.com/gim/journal/v4/n1/full/gim20024a.html

NIH, Genetics Home Reference: SMN1 gene.

See http://ghr.nlm.nih.gov/gene/SMN1

NIH, Genetics Home Reference: SMN1 gene.

See http://ghr.nlm.nih.gov/gene/SMN2

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

Prior, T.W. & Russman, B.S., (2000), “Spinal Muscular Atrophy,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1352/

Recombine Website. Spinal Muscular Atrophy: SMN1 linked.

See https://recombine.com/diseases/spinal-muscular-atrophy-smn1-linked




Spinal Muscular Atrophy (UBA1)


Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes, most commonly the SMN1 gene. However, it can also be caused by the UBA1 gene, which encodes for the ubiquitin-activating enzyme E1. SMA from UBA1 is referred to as X-linked SMA, as the gene resides on the X chromosome. This ubiquitin-activating enzyme breaks down unwanted proteins which can damage motor neurons responsible for muscle movement. Babies usually exhibit muscle weakness from birth, and are prone to lung disease and bone fractures. Typically, breathing becomes progressively more difficult, and very few survive childhood. Other types of SMA are the result of SMN1 mutations. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, so tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of spinal muscular atrophy (all types) is around 1 in 6,000 to 1 in 10,000 births. However, SMA caused by the UBA1 gene is very rare. Less than 20 families with this condition have been found by researchers. The gene is on the Xchromosome, which affects males far more than females, as males only have one Xchromosome, and are affected by the disease if the chromosome carries a mutated UBA1 gene. For females, both X-chromosomes need to have a mutated UBA1 gene for the disease to occur, which is very unlikely. A woman with a mutated UBA1 gene on one X-chromosome can act as a carrier without showing symptoms.

Sources

Baumbach-Reardon, L. et al. (2008), “Spinal Muscular Atrophy, X-Labelled Infantile,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK2594/

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

NIH, Genetics Home Reference: UBA1 gene.

See http://ghr.nlm.nih.gov/gene/UBA1




Spinal Muscular Atrophy (VAPB)


Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes, usually the SMN1 gene. However, a few cases of adult-onset SMA have been linked to mutations in the VAPB gene, which produces the protein named “VAMP-associated protein B and C.” Those with SMA from VAPB mutations begin to suffer from progressive muscle weakness, and may have cramps, tremors, and swallowing or breathing difficulties. Symptoms can begin at any age between 20 and 60. SMA from SMN1 defects is divided into different types, types 1-4: all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, so tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of spinal muscular atrophy (all types) is around 1 in 6,000 to 1 in 10,000 births. However, the adult-onset form related to the VAPB gene is much rarer, having only been found in a small number of families. The faulty gene is transmitted in an autosomal dominant manner, typically requiring at least one affected parent. If an asymptomatic parent died at a relatively young age, it is possible that the disease did not have time to present itself. The faulty gene is also associated with some cases of ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig’s disease.

Sources

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

NIH, Genetics Home Reference: VAPB gene.

See http://ghr.nlm.nih.gov/gene/VAPB

Nishimura, A.L. et al. (2004), “A Mutation in the Vesicle-Trafficking Protein VAPB Causes Late-Onset Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis,” American Journal of Human Genetics, 75, 822-831.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182111/

Richieri-Costa, A. et al. (1981), “Autosomal dominant late adult spinal muscular atrophy, type Finkel,” American Journal of Medical Genetics, 9, 119-128.

See http://www.ncbi.nlm.nih.gov/pubmed/7258225




Spinal Muscular Atrophy (DYNC1H1)


Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes, usually the SMN1 gene. However, in a few cases SMA is caused by mutations in the DYNC1H1 gene. This gene encodes for a protein that is part of a motor protein complex called dynein. If dynein is ineffective in moving proteins and other materials around cells, the motor neurons in the spinal cord may not function properly. The SMA caused by the DYNC1H1 gene causes muscle weakness only in the lower limbs, particularly the thigh muscles, so is referred to as spinal muscular atrophy, lower extremity, dominant (SMA-LED). Sufferers find it difficult to climb stairs, get up from a chair, or walk long distances. The disease normally first occurs in childhood, but is not life-threatening. SMA caused by SMN1 defects is divided into different types; types 1-4 of SMA all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, and tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of spinal muscular atrophy (all types) is around 1 in 6,000 to 1 in 10,000 births. However, SMA from DYNC1H1 mutations only affects a small number of families. Unlike SMN1 defects, which are autosomal recessive, the mutations in DYNC1H1 are autosomal dominant. Typically, autosomal dominant inheritance require at least one affected parent.

Sources

NIH, Genetics Home Reference: DYNC1H1 gene.

See http://ghr.nlm.nih.gov/gene/DYNC1H1

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

Harms, M.B. et al. (2010), “Dominant spinal muscle atrophy with lower extremity predominance,” Neurology, 75, 539-546.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918478/





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