There are several autosomal recessive genetic conditions that occur at a higher incidence in the Ashkenazi Jewish population. These conditions include Canavan disease, Gaucher disease, Tay-Sachs disease, familial dysautonomia, and cystic fibrosis. It is estimated that between 1 in 4 and 1 in 5 individuals of Ashkenazi Jewish ancestry are carriers for one of these disorders.
|Condition||Disease Incidence*||Carrier Frequency*|
*in the Ashkenazi Jewish population.
Table modified from GeneReviews (available at www.genetests.org)
Canavan disease (CD) is a severe and progressive leukodystrophy characterized by macrocephaly, developmental delay, and progressive neuromuscular decline. CD is caused by specific mutations in the ASPA gene.
Gaucher disease (GD) is one of the most prevalent lysosomal storage diseases. GD encompasses a wide variety of clinical features ranging from perinatal lethal to individuals that are relatively asymptomatic until later in life. Typical features include bony abnormalities (lytic lesions), hepatosplenomegaly, anemia, thrombocytopenia, and lung disease. Certain forms of GD have neurological sequelae. GD is caused by four common mutations in the GBA gene.
Tay-Sachs disease (TSD) is a neurodegenerative lysosomal storage disorder caused by deficiency of the hexosaminidase A enzyme. Classic TSD is characterized by progressive weakness, loss of motor skills, seizures, blindness, and early death, with features typically presenting prior to 4 years of age. TSD is caused by specific mutations in the HEXA gene.
Familial dysautonomia (FD) is an autosomal recessive progressive condition that has features of both sensory and autonomic dysfunction. Clinical features include hypotonia during infancy with decreased or absent deep tendon reflexes, decreased taste, alacrima, gastrointestinal dysfunction, recurrent pneumonia, reduced sensitivity to pain and temperature, and cardiovascular instability. FD is caused by a specific mutation in the IKBKAP gene.
Cystic fibrosis (CF) is an autosomal recessive genetic condition that affects epithelia of the respiratory tract, exocrine pancreas, intestine, male genital tract, hepatobiliary system, and exocrine sweat glands, resulting in complex multisystem disease. Disease expression is variable and can range from mild pulmonary and pancreatic involvement to severe progressive obstructive lung disease with pancreatic insufficiency and early mortality. CFTR targeted mutation analysis is performed. For further information regarding specific mutations please [click here].
Practice guidelines published by the American College of Obstetrics and Gynecology (ACOG), recommend that all individuals of Ashkenazi Jewish ancestry should be offered carrier screening for Canavan disease, cystic fibrosis, familial dysautonomia, and Tay-Sachs disease. (ACOG Committee Opinion Number 442; 2009)
- Carrier screening for prenatal patients of Ashkenazi Jewish ancestry.
- Confirmation of a suspected diagnosis of one of the above conditions.
- Family history of one of the above conditions.
- Regions of the genes of interest (ASPA, CFTR, GBA, HEXA, and IKBKAP) are selectively amplified through PCR. For CD, GD, TSD and FD detection, PCR products are analyzed by RFLP. For CFTR mutation detection please see targeted mutation panel for further information.
- The above-mentioned genes can be performed as a 5-gene panel or individually.
- The following mutations are analyzed::
- Canavan disease: Y231X, E285A;
- Cystic fibrosis: Targeted mutation panel.
- Gaucher disease: N370S, 84GG, L444P, IVS2(+1) G->A;
- Familial dysautonomia: IVS20+6T->G.
- Tay-Sachs disease: 1277insTATC, G269S and IVS12(+1) G->C
- 8-10 days (full panel or one individual test)
- Blood: A single tube with 1-5 mL whole blood in EDTA (lavender top).
- Shipping: Store blood at 4°C until shipment. Ship at ambient temperature in an insulated container via overnight delivery within 96 hours of collection.
211 S. Main Street
Orange, CA 92868
- Molecular Testing Requisition Form (Click Here)
- Molecular Diagnostic Consent Form:
This interpretation is based on the clinical and family information provided and the current understanding of molecular genetics of the above diseases.
- Ashkenazi Jewish Panel (Cystic fibrosis, Canavan disease, Gaucher disease, Tay-Sachs disease, and familial dysautonomia):
- CPT: 81212
- Canavan disease only:
- CPT: 81200
- Gaucher disease only:
- Tay-Sachs disease only:
- CPT: 81255
- Familial dysautonomia only:
- CPT: 81260
- Cystic fibrosis only:
- CPT: 81220
- “ACOG Committee Opinion. No. 442: Preconception and Prenatal Carrier Screening for Genetic Diseases in Individuals of Eastern European Jewish Descent.” Obstetrics and Gynecology 114.4 (2009): 950-953.