title: Heterozygosity for Tay-Sachs disease in non-Jewish Americans with ancestry from Ireland or Great Britain.
abstract: We performed a genetic epidemiological analysis of American non-Jewish people with ancestry from Ireland or Great Britain with regard to heterozgosity for Tay-Sachs disease (TSD). This study was prompted by a recent report that the frequency of heterozygosity for TSD among Irish Americans was 1 in 8, a frequency much higher than that recognised for any other population group. We identified 19 of 576 (3.3%) people of Irish background as TSD heterozygotes by the standard thermolability assay for beta-hexosaminidase A (Hex A) activity. Three of 289 people of non-Irish British Isles background (1%) were also identified as heterozygotes by biochemical testing. Specimens from the biochemically identified Irish heterozygotes were analysed for seven different Hex A alpha subunit gene mutations; three (15.8%) had a lethal +1 IVS-9 G to A mutation, previously noted to be a common mutation among TSD heterozygotes of Irish ancestry. Eight of 19 (42.1%) had one of two benign or pseudodeficiency mutations, and no mutation was found in 42.1% of the heterozygotes analysed. These data indicate that non-Jewish Americans with Irish background have a significantly increased frequency of heterozygosity at the Hex A alpha subunit gene locus, but that approximately 42% of the biochemically ascertained heterozygotes have clinically benign mutations. A pseudodeficiency mutation was identified in one of the three TSD heterozygotes of non-Irish British Isles background; no mutations were found in the other two. The data allow for a frequency estimate of deleterious alleles for TSD among Irish Americans of 1 in 192 to 1 in 52. Non-Jewish Americans with ancestry from Great Britain have a minimal, if any, increase in rate of heterozygosity at the TSD gene locus relative to the general population.
authors.affiliation: Division of Medical Genetics, Shriver Center for Mental Retardation, Waltham, MA 02254, USA.
authors.forename: M
authors.initials: M
authors.lastname: van Bael
authors.forename: M R
authors.initials: MR
authors.lastname: Natowicz
authors.forename: J
authors.initials: J
authors.lastname: Tomczak
authors.forename: E E
authors.initials: EE
authors.lastname: Grebner
authors.forename: E M
authors.initials: EM
authors.lastname: Prence
mesh_terms: D015331:Cohort Studies; D006579:Heterozygote; D054818:Hexosaminidase A; D006801:Humans; D007494:Ireland; D007585:Jews; D013661:Tay-Sachs Disease / Q000201:enzymology / Q000235:genetics*; D006113:United Kingdom; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases