{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:17:21Z","timestamp":1789179441111,"version":"build-2803163510"},"reference-count":26,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1996,10]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1136\/jmg.33.10.829","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"829-832","source":"Crossref","is-referenced-by-count":16,"title":["Heterozygosity for Tay-Sachs disease in non-Jewish Americans with ancestry from Ireland or Great Britain."],"prefix":"10.1136","volume":"33","author":[{"given":"M","family":"van Bael","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M R","family":"Natowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Tomczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E E","family":"Grebner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E M","family":"Prence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1996,10,1]]},"reference":[{"key":"ref_1","first-page":"2839","article-title":"The GM2 gangliosidoses","volume-title":"The metabolic and molecular bases of inherited disease","author":"Gravel, R.A.; Clarke, J.T.R.; Kaback, M.M.; Mahuran, D.; Sandhoff, K.; Suzuki, K.","year":"1995","unstructured":"Gravel RA, Clarke JTR, Kaback MM, Mahuran D, Sandhoff K, Suzuki K. 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Clin Chem 1993;39:1811-14.","journal-title":"Clin Chem"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.33.10.829","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:10:34Z","timestamp":1760764234000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.33.10.829"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,10]]},"references-count":26,"journal-issue":{"issue":"10","published-online":{"date-parts":[[1996,10,1]]},"published-print":{"date-parts":[[1996,10]]}},"alternative-id":["10.1136\/jmg.33.10.829"],"URL":"https:\/\/doi.org\/10.1136\/jmg.33.10.829","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,10]]}}}