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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)793-801
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number4
StatePublished - Oct 1992


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