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Hum Mutat. 1992;1(6):486-90.

An unusual genotype in an Ashkenazi Jewish patient with Tay-Sachs disease.

Author information

1
Laboratory of Biochemistry and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.

Abstract

The Ashkenazi Jewish population is enriched for carriers of a fatal form of Tay-Sachs disease, a recessive inherited disorder caused by mutations in the alpha-chain of the lysosomal enzyme beta-hexosaminidase A. Approximately 20% of the Ashkenazi carriers harbor a splice junction defect while about 78% bear a 4 base pair (bp) insertion. However, the Ashkenazi Jewish patient used in the original description of the 4 bp insertion carried this lesion in only 1 allele and was negative for the splice junction mutation. We cloned the insertion negative allele and by sequence analysis of the exons found a point mutation in exon 11 that results in substitution of Trp392 with a premature termination codon. Nine Ashkenazi Jewish carriers that tested negative for the major and minor mutations as well as for a lesion causing an adult form of Tay-Sachs disease did not carry the base change defect, suggesting that it may be a recent and/or rare mutation. This finding also indicates that screening the Ashkenazi population solely by recombinant DNA methods for the splice junction, 4 bp insertion, and adult mutations may result in occasional false negatives.

PMID:
1301958
DOI:
10.1002/humu.1380010606
[Indexed for MEDLINE]

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