Ashkenazi-Jewish and non-Jewish adult GM2 gangliosidosis patients share a common genetic defect.

摘要

The adult form of Tay-Sachs disease, adult GM2 gangliosidosis, is an autosomal recessive neurological disorder caused by a partial deficiency of beta-hexosaminidase A. We had previously identified, in Ashkenazi-Jewish adult GM2 gangliosidosis patients, a Gly269----Ser mutation in the beta-hexosaminidase alpha-subunit. All of the Ashkenazi patients were found to be compound heterozygotes with an allele containing the Gly269----Ser mutation together with one of the Ashkenazi infantile Tay-Sachs alleles. We have now found the same Gly269----Ser mutation in six adult GM2 gangliosidosis patients from four different non-Jewish families. Genomic DNA from three of the patients, two of whom were brothers, exhibited a hybridization pattern consistent with homozygosity for the Gly269----Ser mutation. The remaining non-Jewish patients were compound heterozygotes of the Gly269----Ser mutation together with an unidentified alpha-subunit mutation. The results demonstrate that individuals homozygous for the Gly269----Ser change can be clinically affected. The same Gly269----Ser mutation in both the Ashkenazi and non-Jewish patients may be the result of a common ancestor, given that the ancestry of these non-Jewish patients, like the Ashkenazim, can be traced to eastern Europe.