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Science 17 March 1989:
Vol. 243. no. 4897, pp. 1471 - 1474
DOI: 10.1126/science.2522679
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Articles

Science, Vol 243, Issue 4897, 1471-1474
Copyright © 1989 by American Association for the Advancement of Science

articles

The mutations in Ashkenazi Jews with adult GM2 gangliosidosis, the adult form of Tay-Sachs disease

R Navon and RL Proia

Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, MD 20892.

The adult form of Tay-Sachs disease, adult GM2 gangliosidosis, is an autosomal recessive disorder that results from mutations in the alpha chain of beta-hexosaminidase A. This disorder, like infantile Tay-Sachs disease, is more frequent in the Ashkenazi Jewish population. A point mutation in the alpha-chain gene was identified that results in the substitution of Gly with Ser in eight Ashkenazi adult GM2 gangliosidosis patients from five different families. This amino acid substitution was shown to depress drastically the catalytic activity of the alpha chain after expression in COS-1 cells. All of these patients proved to be compound heterozygotes of the allele with the Gly to Ser change and one of the two Ashkenazi infantile Tay-Sachs alleles. These findings will aid in the diagnosis and understanding of beta-hexosaminidase A deficiency disorders.


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