Carrier rate of Canavan disease among Ashkenazi Jewish individuals

Canavan Disease (CD) is a severe leukodystrophy prevalent among people of Ashkenazi Jewish extraction. The incidence of CD is unknown although it has been stated to be rare. The human aspartoacylase gene has been cloned and mutation determined in 50 Jewish patients with CD. Four mutations were identified in 99 of 100 alleles. A missense mutation, E285A, accounted for 83% of the alleles; a second mutation, Y231X, was found in 13% of the alleles; two other mutations accounted for 3 alleles. In non-Jewish individuals with CD, 52 alleles were examined and 11 mutations were observed. In order to determine the rate of carriers in the Ashkenazi Jewish population, 2,700 blood specimens from unrelated healthy individuals were studied using a panel of 4 mutations found in Jewish individuals. Genomic DNA was amplified by PCR and analyzed for single strand conformation polymorphism. The mutations identified were confirmed by restriction digestion. Sixty carriers were identified, suggesting a carrier rate of 1:45. Of the 60 carriers, 52 had E285A mutation and 8 had Y231X. The proportion of E285A and Y231X mutations in the Jewish population was 86.7% and 13.3%, respectively, in agreement with the relative distribution seen in patients with CD. These studies are more » being expanded to a larger sample so that other mutations are identified. Our data suggest higher than expected carrier rate for CD in Ashkenazi Jews. It seems that carrier testing for preventive counseling should be applied in the risk population. « less