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. 1992 Oct;51(4):793–801.

A pseudodeficiency allele common in non-Jewish Tay-Sachs carriers: Implications for carrier screening

B L Triggs-Raine, E H Mules, M M Kaback, J S T Lim-Steele, C E Dowling, B R Akerman, M R Natowicz, E E Grebner, R Navon, J P Welch, C R Greenberg, G H Thomas, R A Gravel
PMCID: PMC1682803  PMID: 1384323

Abstract

Deficiency of β-hexosaminidase A (Hex A) activity typically results in Tay-Sachs disease. However, healthy subjects found to be deficient in Hex A activity (i.e., pseudodeficient) by means of in vitro biochemical tests have been described. We analyzed the HEXA gene of one pseudodeficient subject and identified both a C739-to-T substitution that changes Arg247→Trp on one allele and a previously identified Tay-Sachs disease mutation on the second allele. Six additional pseudodeficient subjects were found to have the C739-to-T mutation. This allele accounted for 32% (20/62) of non-Jewish enzyme-defined Tay-Sachs disease carriers but for none of 36 Jewish enzyme-defined carriers who did not have one of three known mutations common to this group. The C739-to-T allele, together with a “true” Tay-Sachs disease allele, causes Hex A pseudodeficiency. Given both the large proportion of non-Jewish carriers with this allele and that standard biochemical screening cannot differentiate between heterozygotes for the C739-to-T mutations and Tay-Sachs disease carriers, DNA testing for this mutation in at-risk couples is essential. This could prevent unnecessary or incorrect prenatal diagnoses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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