Q: Tay-Sachs (HEXA)

Tay-Sachs disease is caused by mutations in the HEXA gene, which encodes for one subunit of the enzyme beta-hexosaminidase A. The enzyme breaks down the toxic substance GM2 ganglioside in the brain and spinal cord. Symptoms usually develop from three months onwards, including loss of motor skills, increasing weakness, and strong startle response. Loss of vision and hearing, seizures, and paralysis normally follow. Life expectancy is 2 to 4 years. Very rare related diseases, which begin later in childhood, adolescence, or early adulthood are also known, but the symptoms are usually much milder. Tay-Sachs is rare in the general population, but tends to be concentrated in various ethnic groups. Among those of Ashkenazi Jewish descent, about 1 in 30 are carriers for the disease. There is also a high level of carriers in the Acadian (Cajun) population of Louisiana, and among French Canadians. However, extensive genetic counseling has led to a large reduction in the number of live births over recent decades. The faulty gene is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene copy. Sources Kaback, M.M. & Desnick, R.J. (1999), “Hexosaminidase A Deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet]. See http://www.ncbi.nlm.nih.gov/books/NBK1218/ NIH, Genetics Home Reference: HEXA gene. See http://ghr.nlm.nih.gov/gene/HEXA NIH, Genetics Home Reference: Tay-Sachs Disease. See http://ghr.nlm.nih.gov/condition/tay-sachs-disease Recombine Website. Tay-Sachs Disease. See https://recombine.com/diseases/taysachs-disease

Q: Fanconi Anemia: Type A (FANCA)

Fanconi Anemia can be caused by defects in a number of genes, one of which is FANCA. This gene is involved in producing a protein involved in DNA repair, which it carries out via the so-called Fanconi anemia pathway. If the protein fails to function, DNA repair will not be carried out as normal, which can lead to many abnormalities, particularly affecting the bone marrow and blood cells. Patients have anemia and tend to suffer from infections. They are much more at risk of leukemia and other cancers than the general population. The majority of patients have one or more physical abnormalities, although a large minority are physically normal. A wide range of physical problems are possible. Common issues include short statue, unusual skin pigmentation, misshapen thumbs, microcephaly, eye defects, and deformed kidneys or genitals. The majority of those with the disease die before the age of 30. The overall incidence of Fanconi anemia is roughly 1 in 160,000, of which about 60- 70% are due to defects in the FANCA gene. Some populations, such as Spanish Roma, black South Africans, and Ashkenazi Jews, are at greater risk of the disease. Fanconi anemia type A is inherited in an autosomal recessive manner, typically requiring both parents to carry a faulty gene asymptomatically. Sources Alter, B.P. & Kupfer, G (2002), “Fanconi Anemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet]. See http://www.ncbi.nlm.nih.gov/books/NBK1401/ NIH, Genetics Home Reference: FANCA gene. See http://ghr.nlm.nih.gov/gene/FANCA NIH, Genetics Home Reference: Fanconi Anemia. See http://ghr.nlm.nih.gov/condition/fanconi-anemia Recombine Website: Fanconi Anemia Type A. See https://recombine.com/diseases/fanconi-anemia-type-a

Q: 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

Q: What is Genetics?

Genetics is the study of heredity and the variations of inherited characteristics. More specifically, genetics is the study of how physical or mental characteristics are passed down from one generation to the next generation. DNA is the instruction manual found in every cell in our body. It is written in a language with only four letters, ATCG. Each person’s DNA is roughly 6 billion letters long. A gene is a small unit within the DNA that codes for a specific action in the body. As an analogy, if the DNA is an encyclopedia, then genes are specific entries inside the encyclopedia.

Q: 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

Question 1

Cystic Fibrosis (CFTR)

Accepted Answer

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

Question 2

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

Accepted Answer

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

Question 3

Marfan Syndrome

Accepted Answer

Marfan syndrome is caused by mutations in the FBN1 gene. These lead to abnormalities in the protein fibrillin, which is an essential component of connective tissues. The severity of the symptoms differs widely between different individuals with the defective gene. The syndrome often leads to eye defects, such as lens displacement and myopia. There is an increased risk of retinal detachment, glaucoma, and cataracts. Cardiovascular defects, such as an enlarged aorta and heart valve problems, are common, and can be life threatening. Medication, typically beta blockers, or surgery may be needed to reduce the risk of serious heart failure. Musculoskeletal disorders often occur: these include loose joints, protrusion or indentation of the sternum, and curvature of the spine. Those with the syndrome tend to be unusually tall and thin. Among the general population the risk of having Marfan’s syndrome is about 1 in 5,000, although a parent with the syndrome has a 50:50 risk of their child inheriting the faulty copy of the gene, due to its nature as an autosomal dominant disorder. The disease seems to be spread evenly among all ethnic groups.
 
Sources
NIH, Genetics Home Reference: Marfan Syndrome. See http://ghr.nlm.nih.gov/condition/marfan-syndrome
 
National Center for Biotechnology: Marfan Syndrome. See http://www.ncbi.nlm.nih.gov/books/NBK1335/on go to app settings and press "Manage Questions" button.

Question 4

What is PrevenTest testing?

Accepted Answer

PreventTest detects mutations (defects in the genes) that are linked to many of the most common cancers. These mutations can unknowlingly be passed from parent to child. PrevenTest screening is for patients with and without cancer. For patients with cancer, it can tell you more about your cancer and the options you have for treatment. For patients without cancer, it can inform you of your potential risks.

Question 5

Niemann-pick Disease Type C1 (NPC1)

Accepted Answer

Niemann-Pick Disease Type C1 is caused by mutations in the NPC1 gene. This gene is involved in producing a protein involved in the transportation of lipids, including cholesterol. Mutations in the NPC2 gene cause similar effects (Type C2). Symptoms of Niemann Pick C1 typically develop in early childhood, but can first appear in adults. Muscle weakness and ataxia (poor control of movements, etc.) become gradually apparent, along with liver disease, seizures (in some cases), and progressive mental deterioration. Patients are often unable to move their eyes vertically (vertical supranuclear gaze palsy). Swallowing and speech deteriorate progressively, leading to a complete inability to ingest food. Respiratory failure may also occur. Most patients die in their 20’s or 30’s. When the disease first appears in adulthood, psychiatric symptoms tend to predominate. The total incidence of Niemann-Pick disease Type C is around 1 in 120,000 births. About 90% are due to the NPC1 gene. The disease is more common in some ethnic groups, such as Hispanics whose ancestors lived in the upper Rio Grande valley. The defective genes are inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.
Sources
Millat, G. et al, (1999), “Niemann-Pick C1 disease: the I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype,” American Journal of Human Genetics, 65, 1321-1329.
See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288284/
NIH, Genetics Home Reference: NCP1 gene.
See http://ghr.nlm.nih.gov/gene/NPC1
NIH, Genetics Home Reference: Niemann-Pick Disease.
See http://ghr.nlm.nih.gov/condition/niemann-pick-disease
Patterson, M. (2000), “Niemann-Pick Disease Type C,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1296/
Recombine Website: Niemann-Pick Disease Type C1.
See https://recombine.com/diseases/niemann-pick-disease-type-c1

Question 6

Long QT Syndrome 5 (KCNE1)

Accepted Answer

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

Question 7

Tay-Sachs (HEXA)

Accepted Answer

Tay-Sachs disease is caused by mutations in the HEXA gene, which encodes for one subunit of the enzyme beta-hexosaminidase A. The enzyme breaks down the toxic substance GM2 ganglioside in the brain and spinal cord. Symptoms usually develop from three months onwards, including loss of motor skills, increasing weakness, and strong startle response. Loss of vision and hearing, seizures, and paralysis normally follow. Life expectancy is 2 to 4 years. Very rare related diseases, which begin later in childhood, adolescence, or early adulthood are also known, but the symptoms are usually much milder. Tay-Sachs is rare in the general population, but tends to be concentrated in various ethnic groups. Among those of Ashkenazi Jewish descent, about 1 in 30 are carriers for the disease. There is also a high level of carriers in the Acadian (Cajun) population of Louisiana, and among French Canadians. However, extensive genetic counseling has led to a large reduction in the number of live births over recent decades. The faulty gene is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.
Sources
Kaback, M.M. & Desnick, R.J. (1999), “Hexosaminidase A Deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1218/
NIH, Genetics Home Reference: HEXA gene.
See http://ghr.nlm.nih.gov/gene/HEXA
NIH, Genetics Home Reference: Tay-Sachs Disease.
See http://ghr.nlm.nih.gov/condition/tay-sachs-disease
Recombine Website. Tay-Sachs Disease.
See https://recombine.com/diseases/taysachs-disease

Question 8

Maple Syrup Urine Disease Type 1A (BCKDHA)

Accepted Answer

Maple syrup urine disease (MSUD) can be caused by mutations in a number of different genes, such as the BCKDHA gene. The BCKDHA gene encodes for the alpha subunit of the enzyme complex known as branched-chain alpha-keto acid dehydrogenase (BCKD), which is essential for the breakdown of branched chain amino-acids (leucine, isoleucine, and valine). Maple syrup urine disease is named due the sweet “maple syrup” smell from the urine of those with the disease. In the most common form of MSUD, untreated babies suffer from poor feeding and vomiting, followed by poor breathing, lethargy, and seizures. Death normally occurs within a few weeks of birth. Treatment is possible using special formula milk, followed by a special diet as an infant becomes older. However, it is difficult to always balance the amount of branched chain amino acids in the diet, since a small amounts must be supplied to maintain health. As they grow up, those with the condition tend to suffer from movement disorders, such as tremors, and various mental problems such as ADHD, low intelligence, autism, depression, and anxiety. In a minority of cases, the disease first shows itself later in infancy or during childhood, rather than immediately after birth. Some children suffer from an intermittent form of MSUD, where they appear normal most of the time, but attacks of the disease can be triggered by infections, stress, etc. Both the common form of the disease and the less severe forms can occur with defects in the BCKDA (Type 1A), BCKDB (Type 1B), and DBT (Type 2) genes; there is not a simple relation between severity and which gene is the cause. All types of Maple syrup urine disease occurs in about 1 in 185,000 live births worldwide. However, it is much more prevalent in old order Amish (BCKDHA defects) and Ashkenazi Jewish families (BCKDHB defects). The frequency of the disease reaches 1 in 380 live births in some old order Amish communities. The faulty gene is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.
Sources
Edelmann, L. et al. (2001), “Maple syrup urine disease: identification and carrierfrequency determination of a novel founder mutation in the Ashkenazi Jewish population,” American Journal of Human Genetics, 69, 863-868.
See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226071/
NIH, Genetics Home Reference: BCKDHA gene.
See http://ghr.nlm.nih.gov/gene/BCKDHA
NIH, Genetics Home Reference: Maple syrup urine disease.
See http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease
 Strauss, K.A. et al. (2006), “Maple Syrup Urine Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1319/
Recombine Website. Maple Syrup Urine Disease Type 1A.
See https://recombine.com/diseases/maple-syrup-urine-disease-type-1a

Question 9

Usher Syndrome Type 1B (MYO7A)

Accepted Answer

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

Question 10

Fanconi Anemia: Type A (FANCA)

Accepted Answer

Fanconi Anemia can be caused by defects in a number of genes, one of which is FANCA. This gene is involved in producing a protein involved in DNA repair, which it carries out via the so-called Fanconi anemia pathway. If the protein fails to function, DNA repair will not be carried out as normal, which can lead to many abnormalities, particularly affecting the bone marrow and blood cells. Patients have anemia and tend to suffer from infections. They are much more at risk of leukemia and other cancers than the general population. The majority of patients have one or more physical abnormalities, although a large minority are physically normal. A wide range of physical problems are possible. Common issues include short statue, unusual skin pigmentation, misshapen thumbs, microcephaly, eye defects, and deformed kidneys or genitals. The majority of those with the disease die before the age of 30. The overall incidence of Fanconi anemia is roughly 1 in 160,000, of which about 60- 70% are due to defects in the FANCA gene. Some populations, such as Spanish Roma, black South Africans, and Ashkenazi Jews, are at greater risk of the disease. Fanconi anemia type A is inherited in an autosomal recessive manner, typically requiring both parents to carry a faulty gene asymptomatically.
Sources
Alter, B.P. & Kupfer, G (2002), “Fanconi Anemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1401/
NIH, Genetics Home Reference: FANCA gene.
See http://ghr.nlm.nih.gov/gene/FANCA
NIH, Genetics Home Reference: Fanconi Anemia.
See http://ghr.nlm.nih.gov/condition/fanconi-anemia
Recombine Website: Fanconi Anemia Type A.
See https://recombine.com/diseases/fanconi-anemia-type-a

Question 11

Nonsyndromic Hearing Loss & Deafness (COL11A2)

Accepted Answer

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

Question 12

What is Genetics?

Accepted Answer

Genetics is the study of heredity and the variations of inherited characteristics. More specifically, genetics is the study of how physical or mental characteristics are passed down from one generation to the next generation. DNA is the instruction manual found in every cell in our body. It is written in a language with only four letters, ATCG. Each person’s DNA is roughly 6 billion letters long. A gene is a small unit within the DNA that codes for a specific action in the body. As an analogy, if the DNA is an encyclopedia, then genes are specific entries inside the encyclopedia.

Question 13

Long QT Syndrome 6 (KCNE2)

Accepted Answer

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

Question 14

What is hereditary cancer?

Accepted Answer

Hereditary cancer syndrome is when a person has a mutation in their genes that puts them at increased risk of developing cancer. This mutation can be passed down from parent to child.

Question 15

Usher Syndrome Type 1F (PCDH15)

Accepted Answer

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

Question 16

Ehlers-Danlos Syndrome Type 4

Accepted Answer

Ehlers-Danlos Syndrome Type 4 is caused by mutations in the COL3A1 gene, which is one of a number of genes that control collagen production. The skin of those with the syndrome tends to bruise very easily. Blood vessels, the bowel, and the uterus have a high risk of perforations. Pregnancy is particularly risky for women with the syndrome. Sufferers tend to have highly visible blood vessels, particularly on the chest, and thin skin. The median age of death is about 48. The disease is autosomal dominant which typically requires at least one affected parent, and has a 50:50 chance of having the defect if one parent is affected. The occurrence of the syndrome is approximately 1 in 250,000 among the general population, and is equally prevalent among different ethnic groups.
Sources
The National Center for Biotechnology regarding Ehlers-Danlos Syndrome Type 4
See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971255/
R. Jindel, A. Choong, D. Arul, S. Dhanjil, J. Chataway, N.J.W. Cheshire, “Vascular Manifestations of Type IV Ehlers–Danlos Syndrome” (2005).
See  http://www.ejvesextra.com/article/S1533-3167(05)00047-6/fulltext

Question 17

What is DNA Sequencing?

Accepted Answer

DNA sequencing is a tool used to discover the precise content and order of the genetic information encoded in DNA. The potential for medical use of DNA sequencing information is incredibly high, giving both doctors and patients key information to make more informed medical decisions.

Question 18

Cystic Fibrosis (SCNN1A)

Accepted Answer

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

Question 19

Canavan Disease (ASPA) ures in my FAQ?

Accepted Answer

Canavan disease is a disease affecting the brain, caused by defects in the ASPA gene. The gene encodes for the enzyme aspartoacylase, whose function is to decompose excess N-acetyl-L-aspartic acid (NAA) in the brain. If the enzyme fails to function, excess NAA interferes with the development of the myelin sheath, the insulating covering around axons which functions to increase speed of neural transmission. The most common form of Canavan Disease, the neonatal or infantile form, causes a failure to develop normal motor skills. They suffer from macrocephaly, hypotonia, and often irritability. Seizures and difficulty swallowing may occur. Children rarely survive beyond their teens, and many die earlier. A milder form of the disease, the juvenile form, sometimes occurs. This is associated with slower than normal development of speech and motor skills, but does not normally lead to severe symptoms or a shortened lifespan. Canavan disease is most common in those of Ashkenazi Jewish descent, where it is estimated to occur in 1 in 6,400 to 1 in 13,500 births. The incidence in the general population is much lower, but accurate estimates are not available. The disease is inherited as autosomal recessive, which typically requires both parents to be carriers of the faulty gene, most likely asymptomatically.
Sources
Matalon, R. & Michals-Matalon, K. (1999), “Canavan Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1234/
NIH, Genetics Home Reference: ASPA gene.
See http://ghr.nlm.nih.gov/gene/ASPA
NIH, Genetics Home Reference: Canavan disease.
See http://ghr.nlm.nih.gov/condition/canavan-disease

Question 20

Maple Syrup Urine Disease Type 1B (BCKDHB)

Accepted Answer

Maple syrup urine disease (MSUD) can be caused by mutations in a number of different genes, such as the BCKDHB gene. The BCKDHB gene encodes for the beta subunit of the enzyme complex known as branched-chain alpha-keto acid dehydrogenase (BCKD), which is essential for the breakdown of branched chain amino-acids (leucine, isoleucine, and valine). Maple syrup urine disease is named due the sweet “maple syrup” smell from the urine of those with the disease. In the most common form of MSUD, untreated babies suffer from poor feeding and vomiting, followed by poor breathing, lethargy, and seizures. Death normally occurs within a few weeks of birth. Treatment is possible using special formula milk, followed by a special diet as an infant becomes older. However, it is difficult to always balance the amount of branched chain amino acids in the diet, since a small amounts must be supplied to maintain health. As they grow up, those with the condition tend to suffer from movement disorders, such as tremors, and various mental problems, such as ADHD, low intelligence, autism, depression, and anxiety. In a minority of cases, the disease first shows itself later in infancy or during childhood, rather than immediately after birth. Some children suffer from an intermittent form of MSUD, where they appear normal most of the time, but attacks of the disease can be triggered by infections, stress, etc. Both the common form of the disease and the less severe forms can occur with defects in the BCKDA (Type 1A), BCKDB (Type 1B), and DBT (Type 2) genes; there is not a simple relation between severity and which gene is the cause. Maple syrup urine disease (all types) occurs in about 1 in 185,000 live births worldwide. However, it is much more prevalent in old order Amish (BCKDHA defects) and those of Ashkenazi Jewish descent (BCKDHB defects). The faulty gene is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.
Sources
Edelmann, L. et al. (2001), “Maple syrup urine disease: identification and carrierfrequency determination of a novel founder mutation in the Ashkenazi Jewish population,” American Journal of Human Genetics, 69, 863-868.
See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226071/
NIH, Genetics Home Reference: BCKDHB gene.
See http://ghr.nlm.nih.gov/gene/BCKDHB
NIH, Genetics Home Reference: Maple syrup urine disease.
See http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease
Recombine Website. Maple Syrup Urine Disease Type 1B.
See https://recombine.com/diseases/maple-syrup-urine-disease-type-1b
Strauss, K.A. et al. (2006), “Maple Syrup Urine Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1319/

Question 21

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

Accepted Answer

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/

Question 22

Modification of the Severity of Spinal Muscular Atrophy (SMN2)

Accepted Answer

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

Question 23

Niemann Pick Disease: Type C2 (NPC2)

Accepted Answer

Niemann-Pick Disease Type C2 is caused by mutations in the NPC2 gene. This gene is involved in producing a protein involved in the transportation of lipids, including cholesterol. Mutations in the NPC1 gene cause similar effects (Type C1, which is much more common). Symptoms of Niemann Pick C2 typically develop in early childhood, but can first appear in adults. Muscle weakness and ataxia (poor control of movements, etc.) become gradually apparent, along with liver disease, seizures (in some cases), and progressive mental deterioration. Sufferers are often unable to move their eyes vertically (vertical supranuclear gaze palsy). Swallowing and speech deteriorate progressively, leading to a complete inability to ingest food. Respiratory failure can also occur. Early death is likely, although some sufferers live for many decades. When the disease first appears in adulthood, psychiatric symptoms tend to predominate. The total incidence of Niemann-Pick disease Type C is around 1 in 120,000 births, translating to 2,500 occurrences in the USA. About 4-5% are due to the NPC2 gene. The defective genes are inherited in an autosomal recessive manner, typically requiring both parents to carry the faulty gene asymptomatically.
Sources
NIH, Genetics Home Reference: NCP2 gene.
See http://ghr.nlm.nih.gov/gene/NPC2
NIH, Genetics Home Reference: Niemann-Pick Disease.
See http://ghr.nlm.nih.gov/condition/niemann-pick-disease
Patterson, M. (2000), “Neimann-Pick Disease Type C,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1296/
Recombine Website: Niemann-Pick Disease Type C2.
See https://recombine.com/diseases/niemann-pick-disease-type-c2

Question 24

Fanconi Anemia: Type C (FANCC)

Accepted Answer

Fanconi Anemia can be caused by defects in a number of genes, one of which is FANCC. This gene is involved in producing a protein involved in DNA repair, which it carries out via the so-called Fanconi anemia pathway. If the protein fails to function, DNA repair will not be carried out as normal, which can lead to many abnormalities, particularly affecting the bone marrow and blood cells. Sufferers have anemia and tend to suffer from infections. They are much more at risk of leukemia and other cancers than the general population. The majority of sufferers have one or more physical abnormalities, although a large minority are physically normal. A wide range of physical problems are possible. Common issues include short statue, unusual skin pigmentation, misshapen thumbs, microcephaly, eye defects, and deformed kidneys or genitals. The majority of those with the disease die before the age of 30. The overall incidence of Fanconi anemia is roughly 1 in 160,000, of which about 14% are due to defects in the FANCC gene. Some populations, such as Spanish Roma, black South Africans, and Ashkenazi Jews, are at greater risk of the disease. There is high incidence of Fanconi anemia type C in the latter community, the carrier rate being about 1 in 100. Fanconi anemia type C is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.
Sources
Alter, B.P. & Kupfer, G (2002), “Fanconi Anemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1401/
NIH, Genetics Home Reference: FANCC gene.
See http://ghr.nlm.nih.gov/gene/FANCC
NIH, Genetics Home Reference: Fanconi Anemia.
See http://ghr.nlm.nih.gov/condition/fanconi-anemia
Recombine Website: Fanconi Anemia Type C.
See https://recombine.com/diseases/fanconi-anemia-type-c

Question 25

Familial Thoracic Aortic Aneurysm and Dissection (ACTA2)

Accepted Answer

Familial TAAD can be caused by mutations in the ACTA2 gene. This gene accounts for around 10-20% of cases of familial TAAD. The gene encodes for the protein α-2 actin, which is a component of smooth muscle cells in arterial walls. Along with the ACTA2 gene, other known and unknown genes can also cause familial TAAD. In patients with TAAD, the aorta increases in diameter, which may cause dissection, or blood flowing through the artery wall following a tear. Rupture of the artery may follow, often leading to rapid death. Surgery is often required where a significant thoracic aortic aneurysm occurs. Families with ACTA2 abnormalities are also more prone to occlusive vascular disease and livedo reticularis, a skin disease. With proper management, life expectancy for those with familial TAAD can approach that of the general population. The ACTA2 gene defects that cause familial TAAD are autosomal dominant. Typically, an affected person has one affected parent. However, it is possible for the defective gene to be carried without any TAAD occurring in a situation known as reduced penetrance. Overall, familial TAAD is estimated to cause roughly 20% of thoracic aortic aneurysms and dissections. Approximately 10,000 deaths per year occur due to TAAD in the USA; about 2,000 will be due to familial TAAD, giving around 200-400 deaths per year from ACTA2 defects, out of an overall USA total of around 2.6 million (0.01 to 0.02% of total deaths).
Sources
NIH, Genetics Home Reference: Familial thoracic aortic aneurysm and dissection.
See https://ghr.nlm.nih.gov/condition/familial-thoracic-aortic-aneurysm-and-dissection

Question 26

What is Next-Generation Sequencing?

Accepted Answer

Next-Generation sequencing (NGS), or Next-Gen sequencing, is a specific sequencing technique that has taken the research world by storm since its inception in the early 2000’s. With its ability to sequence quickly and efficiently, NGS is the perfect technique to provide medical professionals with important genetic information about their patients in a timely manner.

Question 27

Maple Syrup Urine Disease Type II (DBT)

Accepted Answer

Maple syrup urine disease (MSUD) can be caused by mutations in a number of different genes, such as the DBT gene. The DBT gene encodes for the E2 component of the enzyme complex known as branched-chain alpha-keto acid dehydrogenase (BCKD), which is essential for the breakdown of branched chain amino-acids (leucine, isoleucine, and valine). Maple syrup urine disease is named due the sweet “maple syrup” smell from the urine of those with the disease. In the most common form of MSUD, untreated babies suffer from poor feeding and vomiting, followed by poor breathing, lethargy, and seizures. Death normally occurs within a few weeks of birth. Treatment is possible using special formula milk, followed by a special diet as an infant becomes older. However, it is difficult to always balance the amount of branched chain amino acids in the diet, since a small amounts must be supplied to maintain health. As they grow up, those with the condition tend to suffer from movement disorders, such as tremors, and various mental problems such as ADHD, low intelligence, autism, depression, and anxiety. In a minority of cases, the disease first shows itself later in infancy or during childhood, rather than immediately after birth. Some children suffer from an intermittent form of MSUD, where they appear normal most of the time, but attacks of the disease can be triggered by infections, stress, etc. Both the most common form of the disease and the less severe forms can occur with defects in the BCKDA (Type 1A), BCKDB (Type 1B), and DBT (Type 2) genes; there is not a simple relation between severity and which gene is the cause. All types of Maple syrup urine disease occur in about 1 in 185,000 live births worldwide. However, it is much more prevalent in old order Amish (BCKDHA defects) and those of Ashkenazi Jewish descent (BCKDHB defects). The faulty gene is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.
Sources
Edelmann, L. et al. (2001), “Maple syrup urine disease: identification and carrierfrequency determination of a novel founder mutation in the Ashkenazi Jewish population,” American Journal of Human Genetics, 69, 863-868.
See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226071/
NIH, Genetics Home Reference: DBT gene.
See http://ghr.nlm.nih.gov/gene/DBT
NIH, Genetics Home Reference: Maple syrup urine disease.
See http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease
 Strauss, K.A. et al. (2006), “Maple Syrup Urine Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1319/

Question 28

Spinal Muscular Atrophy (UBA1)

Accepted Answer

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

Question 29

Non-syndromic Deafness (GJB3) (Connexin 31)

Accepted Answer

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

Question 30

Sickle Cell Disease (HBB)

Accepted Answer

Sickle cell disease is caused by mutations in the HBB gene, which encodes for the protein beta-globin, a component of hemoglobin. The main form of the disease is sickle cell anemia, where the red blood cells are bent into a sickle shape. Sickle cells break down more quickly than normal cells, often resulting in anemia. The irregular cell shape tends to block blood vessels, which can lead to pain and ischemia of organs, including strokes. Jaundice and damage to the spleen often occur. In some cases, pulmonary hypertension can occur and lead to heart failure. Other than sickle cell formation, other abnormal forms of hemoglobin can form. The various symptoms of sickle cell anemia shorten live expectancy to about 40 to 60 years. Sickle cell disease tends to be concentrated in particular ethnic groups. About 1 in 500 African Americans have sickle cell disease, while the figure is about 1 in 1,000 to 1 in 1,400 for Hispanic Americans. In all about 100,000 Americans suffer from sickle cell disease. As the population of the USA is around 321 million, this means that about 1 in 3210 Americans has the disease, making it the most common inherited blood disease. The faulty gene is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.
Sources
 Bender M.A. & Seibel, G.D. (2003), “Sickle Cell Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1377/
NIH, Genetics Home Reference: HBB gene.
See http://ghr.nlm.nih.gov/gene/HBB
NIH, Genetics Home Reference: Sickle Cell Disease.
See http://ghr.nlm.nih.gov/condition/sickle-cell-disease
Recombine Website. Sickle Cell Anemia.
See https://recombine.com/diseases/sickle-cell-anemia
US Census Bureau http://www.census.gov/popclock/

Question 31

Long QT Syndrome 1 (KCNQ1)

Accepted Answer

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

Question 32

Usher Syndrome Type 1C (USH1C)

Accepted Answer

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

Question 33

Cystic Fibrosis (SCNN1B)

Accepted Answer

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

Question 34

Fanconi Anemia: Type F (FANCF)

Accepted Answer

Fanconi Anemia can be caused by defects in a number of genes, one of which is FANCF. This gene is involved in producing a protein involved in DNA repair, which it carries out via the so-called Fanconi anemia pathway. If the protein fails to function, DNA repair will not be carried out as normal, which can lead to many abnormalities, particularly affecting the bone marrow and blood cells. Patients have anemia and tend to suffer from infections. They are much more at risk of leukemia and other cancers than the general population. The majority of sufferers have one or more physical abnormalities, although a large minority are physically normal. A wide range of physical problems are possible. Common issues include short statue, unusual skin pigmentation, misshapen thumbs, microcephaly, eye defects, and deformed kidneys or genitals. The majority of those with the disease die before the age of 30. The overall incidence of Fanconi anemia is roughly 1 in 160,000, of which about 2% are due to defects in the FANCF gene. Some populations, such as Spanish Roma, black South Africans, and Ashkenazi Jews, are at greater risk of the disease. Fanconi anemia type F is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.
Sources
Alter, B.P. & Kupfer, G (2002), “Fanconi Anemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1401/
NIH, Genetics Home Reference: FANCF gene.
See http://ghr.nlm.nih.gov/gene/FANCF
NIH, Genetics Home Reference: Fanconi Anemia.
See http://ghr.nlm.nih.gov/condition/fanconi-anemia

Question 35

Will this test tell me if I have cancer?

Accepted Answer

No. A positive result on the cancer screen is not a diagnosis of cancer.

Question 36

Spinal Muscular Atrophy (VAPB)

Accepted Answer

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

Question 37

Congenital Aneurysms (COL4A1)

Accepted Answer

Congenital aneurysms (widening of blood vessels) can be caused by mutations in the COL4A1 gene. This gene codes for the alpha-1 (IV) chain of type IV collagen. Defects in the gene can lead to cerebral aneurysms and strokes, due to a condition known as COL4A1-related brain small vessel disease. Damage to blood vessels can lead to various eye disorders. Defects in the gene can also cause porencephaly (fluid filled areas in the brain). A syndrome known as HANAC, hereditary angiopathy with nephropathy, aneurysms and muscle cramps, may also occur. Here, the kidneys are damaged, eye problems are common, aneurysms may occur in the brain and elsewhere, and the patient suffers frequent muscle cramps. The various conditions caused by COL4A1 defects all give increased risk of premature death, typically from strokes. The defective gene is autosomal dominant. Affected people typically have one affected parent. Diseases caused by defects in the COL4A1 gene are very rare. Less than 100 individuals with such diseases have been identified, all from Europe or North America.
Sources
Natural Institute of Neurological Disorders and Stroke
See  http://www.ninds.nih.gov/disorders/cerebral_aneurysm/detail_cerebral_aneurysms.htm
National Center for Biotechnology regarding mutations of the COLA1 gene
See http://www.ncbi.nlm.nih.gov/books/NBK7046/

Question 38

Fanconi Anemia: Type G (FANCG)

Accepted Answer

Fanconi Anemia can be caused by defects in a number of genes, one of which is FANCG. This gene is involved in producing a protein involved in DNA repair, which it carries out via the so-called Fanconi anemia pathway. If the protein fails to function, DNA repair will not be carried out as normal, which can lead to many abnormalities, particularly affecting the bone marrow and blood cells. Sufferers have anemia and tend to suffer from infections. They are much more at risk of leukemia and other cancers than the general population. The majority of patients have one or more physical abnormalities, although a large minority are physically normal. A wide range of physical problems are possible. Common ones include short statue, unusual skin pigmentation, misshapen thumbs, microcephaly, eye defects, and deformed kidneys or genitals. The majority of those with the disease die before the age of 30. The various types of the disease produce similar symptoms, although there is some evidence that leukemia is more likely to develop with Type G. The overall incidence of Fanconi anemia is roughly 1 in 160,000, of which about 10% are due to defects in the FANCG gene. Some populations, such as Spanish Roma, black South Africans, and Ashkenazi Jews, are at greater risk of the disease. Fanconi anemia type G is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.
Sources
Alter, B.P. & Kupfer, G (2002), “Fanconi Anemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1401/
NIH, Genetics Home Reference: FANCG gene.
See http://ghr.nlm.nih.gov/gene/FANCG
NIH, Genetics Home Reference: Fanconi Anemia.
See http://ghr.nlm.nih.gov/condition/fanconi-anemia
Recombine Website: Fanconi Anemia Type G.
See https://recombine.com/diseases/fanconi-anemia-type-g

Question 39

Long QT Syndrome 3 (SCN5A)

Accepted Answer

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

Question 40

Usher Syndrome Type 2A (USH2A)

Accepted Answer

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

Question 41

Gaucher Disease (GBA)

Accepted Answer

Gaucher Disease is caused by mutations in the GBA gene. This gene encodes for the enzyme beta-glucocerebrosidase, which breaks down the substance glucocerebroside. The buildup of glucocerebroside causes damage to various organs. There are various types of Gaucher disease. Type 1 is the most common, and involves anemia, lung disease, enlargement of the spleen and liver, easy bruising of the skin, and skeletal disorders such as arthritis and high risk of fractures. The nervous system is not affected in type 1 Gaucher disease. Types 2 and 3 involve serious damage to the nervous system, with type 2 being the more aggressive, leading normally to early mortality. A perinatal form of the disease is also known, leading to prompt death after birth. Finally, a cardiovascular form of the disease mainly involves damage to the heart valves. In the general population, Gaucher disease is found in 1 in 60,000 to 1 in 80,000 new births. It is much more prevalent in various ethnic groups. Among those of Ashkenazi Jewish descent, the disease is found in 1 in 855 people (nearly all Type 1), with around 1 in 18 people being carriers. The disease is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.
Sources
Pastores, G.M. & Hughes, D.A. (2000), “Gaucher Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1269/
NIH, Genetic Home Reference: GBA gene.
See http://ghr.nlm.nih.gov/gene/GBA
NIH, Genetics Home Reference: Gaucher.
See http://ghr.nlm.nih.gov/condition/gaucher-disease
Recombine Website. Gaucher Disease.
See https://recombine.com/diseases/gaucher-disease

Question 42

Non-syndromic Deafness (KCNQ4)

Accepted Answer

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/

Question 43

What genes and cancers do you test for?

Accepted Answer

PrevenTest looks at 36+ genes that are linked to 8+ hereditary cancers. These cancers are Breast, Ovarian, Colorectal, Endometrial, Melanoma, Pancreatic, Gastric, Prostate, and other less common cancers.

Question 44

Cystic Fibrosis (CA12)

Accepted Answer

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

Question 45

Why does the sequence of my DNA matter?

Accepted Answer

DNA sequence information is important because it may be an indicator/predictor of future disease, or a disease may be passed on to future children. Prior knowledge of future disease risk or risk for children to inherit a disease may influence the decisions made by you or your doctor. For example, a couple at serious risk to have a child inherit a fatal disease may opt, armed with the knowledge taken from their DNA sequences, to undergo in-vitro fertilization to prevent the birth of a child with a fatal genetic disease. Without the crucial information provided by DNA sequencing, the couple may not have been aware of their risk to have a child with a fatal disease, which may have affected their original reproductive decisions.

Question 46

Maple Syrup Urine Disease Type 3 (Dihydrolipoamide dehydrogenase deficiency) (DLD)

Accepted Answer

Maple syrup urine disease (MSUD) can be caused by mutations in a number of different genes, including the DLD gene. The DLD gene encodes for the enzyme dihydrolipoamide dehydrogenase. This enzyme is involved in a number of different enzyme complexes, including branched-chain alpha-keto acid dehydrogenase (BCKD), which is essential for the breakdown of branched chain amino-acids (leucine, isoleucine, and valine). Maple syrup urine disease is named due the sweet “maple syrup” smell from the urine of those with the disease, although the odor is seldom present in the type 3 disease. In the more common form of MSUD, untreated babies suffer from poor feeding and vomiting, followed by poor breathing, lethargy, and seizures. Death normally occurs within a few weeks of birth, but can be avoided by special formula milk, etc. As they grow up, those with the condition tend to suffer from movement disorders, such as tremors, and various mental problems, such as ADHD, low intelligence, autism, depression, and anxiety. However, in type 3 of maple syrup disease, many other symptoms can be present, since the dihydrolipoamide dehydrogenase enzyme is a component of other enzyme complexes, such as the pyruvate dehydrogenase complex. Lactic acidosis is common in infants with the type 3 disease, giving rise to muscle weakness and lethargy. Type 3 MSUD is vary variable, and in some cases the symptoms of the most common form of MSUD are absent, or their onset delayed. The disease is often episodic, worsening when the body is stressed by an infection, etc. Adult-onset liver disease can occur, which is not a normal symptom of MSUD. All types of Maple syrup urine disease occur in about 1 in 185,000 live births worldwide. Type 3 MSUD is extremely rare, but is most commonly seen in those of Ashkenazi Jewish descent, where it affects about 1 in 40,000 individuals. The faulty gene is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.
Sources
NIH, Genetics Home Reference: Dihydrolipoamide dehydrogenase deficiency.
See http://ghr.nlm.nih.gov/condition/dihydrolipoamide-dehydrogenase-deficiency
NIH, Genetics Home Reference: DLD gene.
See http://ghr.nlm.nih.gov/gene/DLD
NIH, Genetics Home Reference: Maple syrup urine disease.
See http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease
Quinonez, S.C. & Thoene, J.G. (2014), “Dihydrolipoamide dehydrogenase deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK220444/
Strauss, K.A. et al. (2006), “Maple Syrup Urine Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1319/

Question 47

What is NewbornGeneID testing?

Accepted Answer

NewbornGeneID detects gene mutations (defects in the genes) linked to many of the most common and devastating diseases that can be passed unknowingly from parent to child.  Newborn screening is a test for parents and prospective parents that provides information on whether a patient has a gene mutation(s) that are linked to a disease.  The results provide information on the likelihood that a child will inherit one of a number of rare diseases.

Question 48

Phenylketonuria (PAH)

Accepted Answer

Phenylketonuria (PKU) is caused by mutations in the PAH gene. This gene encodes for the enzyme phenylalanine hydroxylase, which breaks down the amino acid phenylalanine. The buildup of phenylalanine causes damage to the body, affecting mainly the brain. If left untreated, those with phenylketonuria suffer from intellectual disability, seizures, delayed development, and psychiatric problems. A musty odor from phenylalanine may be evident. Treatment is by a special low phenylalanine diet, which can allow for normal development if strictly adhered to. There are rarer, less damaging forms of the disease, known as non-PKU hyperphenylalaninemia. Phenylketonuria is found in 1 in 10,000 to 1 in 15,000 new births. Since screening and prompt treatment are almost universal in the USA, the symptoms are very rarely seen. The disease is more common in some ethnic groups, such as Turks (1 in 2,600 births) and Irish (1 in 4,600 births). The condition follows an autosomal recessive pattern, typically requiring both parents to be carriers asymptomatically.
Sources
Mitchell, J.J. (2000), “Phenylalanine hydroxylase deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet].
See http://www.ncbi.nlm.nih.gov/books/NBK1504/
NIH, Genetic Home Reference: PAH gene.
See http://ghr.nlm.nih.gov/gene/PAH
NIH, Genetics Home Reference: Phenylketonuria.
See http://ghr.nlm.nih.gov/condition/phenylketonuria
Recombine Website. Phenylalanine Hydroxylase Deficiency.
See https://recombine.com/diseases/phenylalanine-hydroxylase-deficiency

Question 49

Pendred syndrome (SLC26A4)

Accepted Answer

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

Question 50

What does a "Positive Result" mean?"

Accepted Answer

If your test returns a positive result, it means that we identified a mutation that increases the risk of cancer. The key to proper management of your test results is first to understand the information provided in your report. With this information at hand, you can then fully understand your cancer risk and create a manageable plan to curtail that risk. GeneID’s report will guide you by explaining the genes, diseases or cancers in question, the general and reproductive recommendations, as well as the potential risks to family members, to achieve a holistic perspective of your and your family’s risk.
A positive result on a GeneID Cancer Genetics Panel means that you inherited a faulty gene from either one or both of your parents. This faulty gene, or mutation, increases your risk for one or several types of cancers.
It is important to distinguish between having a mutation and having cancer: if you test positive for a mutation, that does not mean that you have cancer, nor does it mean that you definitely will get cancer.
Risk and Management:
You may have been prompted to take a cancer genetic test after discovering a family history of cancer. Alternatively, you may have had cancer already and want to understand your risk of the cancer returning, or the chance of developing other cancer types. Family history or personal cancer history may increase your cancer risk compared to the general population.

Your testing report provides you information regarding the cancers related to your potential gene mutation. Once you have the results, you can mitigate your cancer risk with several options:
 • Increased screening to catch any potential cancers in their initial stages
 • Certain medications may be prescribed depending on the relevant condition
 • Lifestyle changes, including diet and exercise
 • Surgery
Together with your healthcare provider, one or several of these options may be discussed and implemented to personalize your prevention or treatment.
Family:
Since your results may affect the health of other family members, it is important to discuss and share your results with them. They may decide to consult their healthcare providers to see how your results might affect them, including the option for genetic testing.

Question 51

Spinal Muscular Atrophy (DYNC1H1)

Question 52

Long QT Syndrome 11 (AKAP9)

Question 53

Usher Syndrome Type 1D (CDH23)

Question 54

Familial Thoracic Aortic Aneurysm and Dissection (MYH11)

Question 55

What diseases do you test for?

Question 56

Familial Thoracic Aortic Aneurysm and Dissection (MYLK)

Question 57

Glycogen Storage Disease II (GAA)

Question 58

What should I do if I test positive for a genetic mutation?

Question 59

Arterial Tortuosity Syndrome (SLC2A10)

Question 60

What does a "Negative Result" mean?"

Question 61

What is a hereditary genetic disease?

Question 62

Question 63

Loeys-Dietz Syndrome Type I (TGFBR1)

Question 64

What does it mean if a trait is “dominant”, “recessive” or “X-linked”?"

Resources> Frequently Asked Questions