Carrier testing for seven diseases common in the Ashkenazi Jewish population: implications for counseling and testing

Abstract Objective: To determine carrier detection rates among Ashkenazi Jews with no family history tested for the following autosomal recessive disorders: Tay-Sachs disease (TS), cystic fibrosis (CF), Gaucher’s disease (GD), Fanconi’s anemia Group C (FA-C), Bloom syndrome (BS), Canavan disease (CD), and Niemann-Pick disease type A (NP). Methods: Data from a 28-month period were collated. Samples were analyzed by PCR and dot blot hybridization with ASO probes. The number of mutations analyzed and individuals tested were disease specific: 3 and 5,754 (TS), 70 or 86 and 9,168 (CF), 5 and 5,277 (GD), 1 and 4,132 (FA-C), 1 and 2,425 (BS), 4 and 9,228 (CD), and 3 and 6,187 (NP). Results: Our experience is one of the largest to date with referrals from across the United States. Carrier rates were as expected for TS (1/27), CF (1/24), and GD (1/14); higher than previously reported for FA-C (1/66) and BS (1/80); and lower for CD (1/58) and NP (1/121). Four individuals tested for CF and ten for GD had two mutations, consistent with very mild disease. Conclusion: ACOG guidelines recommend that carrier testing for TS and CD be offered to individuals of Ashkenazi Jewish descent. Similar guidelines are expected for CF. Given the severity of NP, the increased morbidity of FA-C and BS, and the frequency of GD, consideration should be given to offering education and testing for these as well. The carrier frequencies determined here will provide accurate risk revisions for counseling.