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Ashkenazi Jewish Diseases Test


This test is recommended for individuals of Jewish ancestry. It accurately diagnoses ten genetic disorder, as well as accurately determines disease gene carrier status. If two individuals are asymptomatic carriers for the same disorder, there is a 25% risk of having a child affected by the disorder.



What is Jewish Diseases Testing?

The Jewish diseases DNA testing panel tests for ten of the most common genetic diseases in individuals of Ashkenazi Jewish descent and individuals of Central or Eastern European origin. The tests examines mutations found in the following 11 genes: BLM, ASPA, IKBKAP, FANCC, GBA, G6PC, BCKDHA, BCKDHB, MCOLN1, SMPD1 and HEXA, all of which are responsible for causing disease.

What are Jewish Diseases?

The term ‘Jewish diseases’ describes genetic disorders that occur more often in individuals of Jewish descent, compared to the general population. This panel of tests focuses on the genetic diseases that are most common in people of Ashkenazi Jewish descent and people who are of Central and Eastern European origin. These diseases can also affect people of other ethnic backgrounds, but at a lower frequency. For example, Tay Sachs disease is found in 1 in every 3000 infants who are Ashkenazi Jewish descent, but only in 1 in every 320,000 infants in the general population. Some of the diseases tested in this panel, such as Tay-Sachs disease and Niemann-Pick disease, are fatal, whereas treatment options are available for the management of Gaucher disease and maple syrup urine disease. The ten Jewish diseases tested are shown in the table below.

Disease Mutations Identified Description
Bloom Syndrome


2281del6/ins7 mutation in the BLM gene. Most affected Jewish people have this mutation. A disorder characterized by short stature, sun sensitivity, increased cancer risk and genomic instability. It is caused by defective RECQL3, an enzyme involved in repairing DNA damage.


Canavan Disease


Four mutations (E285A, Y231X, IVS2-2A>G and A305E) in the ASPA gene. E285A and Y231X (the most common mutations) and IVS2-2A>G (rare) account for 98% of Jewish cases and only 3% of non-Jewish cases. A305E only accounts for about 1% of Jewish cases, but is more common in non-Jewish cases (40-60%).
A progressive, fatal neurological disorder caused by defective aspartoacylase, an enzyme that breaks down the N-acetyl-L-aspartic acid (NAA) compound. NAA accumulates in the brain of affected people and interferes with the development of the nervous system by progressively breaking down the myelin sheaths, (the white insulating sheath surrounding neurons).


Familial Dysautonomia


Two mutations (IVS20+6T>C and R696P) in the IKBKAP gene. These two mutations occur in 99% of Jewish cases. (IVS20+6T>C is a.k.a c.2204+6T>C). A disorder of the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. This disorder is caused reduced levels of IKK complex-associated protein (IKAP).


Fanconi Anemia Group C


Two mutations (IVS4+4A>T and 322delG) in the FANCC gene. (These two mutations are also known as c.456+4A>T and c.67delG).


A rare, inherited genome instability disorder that leads to increased cancer risk and bone marrow failure. Mutations in at least 15 genes cause Fanconi anemia and protein products of these genes are involved in a process called the Fanconi anemia pathway, which is important for DNA repair. Fanconi anemia group C is the most common form found in people of Ashkenazi Jewish descent and is caused by mutations in FANCC.


Gaucher Disease


Eight mutations in the GBA gene: L444P, N370S, 84insG, IVS2+1G>A, V394L, D409H, delta55bp and R496H. Four of these mutations (L44P, N370S, 84insG and IVS2+1G>A) account for 90% of Ashkenazi Jewish cases.


A lipid storage disease caused by the accumulation of a fatty substance (sphingolipids) in organs and tissues. This accumulation is  due to a defective enzyme, beta-glucocerebrosidase, that is responsible for breaking down glucocerebroside into a sugar (glucose) and a simpler fat molecule (ceramide).


Glycogen Storage Disease Type IA


Two mutations (R83C and Q347X) in the G6PC gene. R83C causes 98% of GSDIA in Ashkenazi Jewish people and Q347X accounts for the remaining 2%.
A disease caused by the toxic accumulation of a complex sugar called glycogen in cells. Glycogen accumulates due to defective glucose-6-phosphatase not metabolizing glucose-6-phosphate properly.


Maple Syrup Urine Disease


The most common mutation (Y438N) in the BCKDHA gene and three mutations (R183P, G278S and E372X) in the BCKDHB gene.


A metabolic disease caused by the inability to properly process three amino acids, leucine, isoleucine and valine, that are present in protein-rich foods like meat, eggs and milk. Mutations in BCKDHA, (encodes the alpha subunit of the BCKAD enzyme complex) and BCKDHB, (encodes the beta subunit of the BCKAD enzyme complex) inhibit this enzyme from breaking down the three amino acids and the accumulation of these compounds is toxic to cells and tissues.


Mucolipidosis Type IV


Two mutations (delta 6.4kb and IVS3-2A>G) in the MCOLN1 gene. These two mutations account for over 95% of mucolipidosis type IV cases in Ashkenazi Jewish people.


A lysosomal storage disorder characterized by delayed development and vision problems. It is caused by defective mucolipin-1, which  is thought to play a role in the transport of fats and proteins within cells, and appears to be essential for the development and the maintenance of the brain and retina.


Niemann-Pick Disease Type A and B


Four mutations (R496L, L302P, fsp330 and delta608) in the SMPD1 gene. The delta608 mutation causes Niemann-Pick disease type B and R496L, fsp330 and L302P account for 95% of the Niemann-Pick type A cases seen in Ashkenazi Jewish individuals.


A lysosomal storage disease caused by defective acid sphingomyelinase. This enzyme is responsible for converting sphingomyelin lipids into ceramide lipids. Mutations that cause type A often results in the complete loss of acid spingomyelinase activity, whereas mutations causing type B allow reduced enzyme activity.


Tay-Sachs Disease


Seven mutations in the HEXA gene. 1278insTATC, IVS12+1G>C, IVS9+1G>A and delta7.6kb all eliminate the production of beta-hexosaminidase A. G269S is associated with adult on-set form of hexosaminidase deficiency. R249W and R247W are called pseudodeficiency mutations as they do not cause Tay-Sachs disease but are associated with reduced activity in enzyme assays. A neurodegenerative diseases caused by defective beta-hexosaminidase A. The defective enzyme is unable to break down GM2 ganglioside and it accumulates to toxic levels, destroying the neurons in the brain and spinal cord and causing the progressive neurodegeneration that is characteristic of Tay-Sachs.



How are Jewish Diseases Inherited?

All of the Jewish diseases tested in this panel are autosomal recessive. We inherit two copies of every autosomal gene, one copy from each parent. To suffer from any of the Jewish diseases tested in this panel you need to inherit two defective copies – one defective copy from each parent.

It is estimated that 1 in 4 Ashkenazi Jews are carriers of a genetic change that can cause a Jewish disease. A carrier is an individual who has one defective copy of the disease gene and one normal copy of the gene. Carriers do not experience any symptoms of the disease, thus may not know that they are a carrier. When two carriers choose to have a child, there is a 25% chance their child will have the genetic disease. There is a 50% chance that their child will also be a carrier of the same genetic disease. Carrier status is important for Jewish diseases because of the high carrier frequency. Carrier screening and genetic counseling is recommended for couples who are of Ashkenazi Jewish descent choosing to have children.

How Common are the Jewish Diseases?

Disease Disease Prevalence in Ashkenazi Jews Carrier Frequency in Ashkenazi Jews
Bloom Syndrome 1 in 40,000-50,000 1 in 100-134
Canavan Disease 1 in 6400-13,500 1 in 40-60
Familial Dysautonomia 1 in 3600-3700 1 in 30-32
Fanconi Anemia Group C 1 in 32,000 1 in 89-100
Gaucher Disease 1 in 900-1000 1 in 7-18
Glycogen Storage Disease Type IA 1 in 16,000-20,000 1 in 64-71
Maple Syrup Urine Disease Type 1A 1 in 50,000 1 in 81-113
Maple Syrup Urine Disease Type 1B 1 in 38,000 1 in 97
Mucolipidosis Type IV 1 in 62,500 1 in 89-127
Niemann-Pick Type A and B 1 in 32,000-40,000 1 in 90-115
Tay-Sachs Disease 1 in 3000-3600 1 in 25-31


DNA Testing for Jewish Diseases

A simple DNA test can be completed to find out whether a person has inherited any defective copies of the 11 genes, (BLM, ASPA, IKBKAP, FANCC, GBA, G6PC, BCKDHA, BCKDHB, MCOLN1, SMPD1 and HEXA) that have been linked to Jewish genetic diseases. Based on the data, your disease carrier status can be determined for each of the ten diseases. Many of these diseases are fatal and carrier testing is useful to determine the likelihood of having an affected child.

Recommended Links:
Aharon-Peretz J et al. (2004). Mutations in the Glucocerebrosidase Gene and Parkinson’s Disease in Ashkenazi Jews. N Engl J Med. 351(19): 1972-1977.

Bargal R et al. (2000). Identification of the gene causing mucolipidosis type IV. Nature Genet. 26: 120-123.

Edelmann L et al. (2002). Carrier Screening for Mucolipidosis Type IV in the American Ashkenazi Jewish Population. Am J Hum Genet. 70(4): 1023-1027.

Kaback MM (2000). Population-based genetic screening for reproductive counseling: the Tay-Sachs disease model. Eur J Pediatr. 159(3): S192-S195.

Levran O et al. (1991). Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients. J Clin Invest. 88(3): 806–810.

Monaghan KG et al. (2008). Technical standards and guidelines for reproductive screening in the Ashkenazi Jewish population. Genet Med. 10(1): 57-72.

Sakallah SA et al. (1994). A new diagnostic test for Gaucher disease suitable for population screening. PCR Methods Appl. 4(1): 1-5.

Strom CM et al. (2004). Molecular screening for diseases frequent in Ashkenazi Jews: Lessons learned from more than 100,000 tests performed in a commercial laboratory. Genet Med. 6(3): 145-152.

Jewish Genetic Disease Consortium (JGDC).