{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:26:40Z","timestamp":1781105200063,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1989,4]]},"abstract":"<jats:p>Chronic and adult-onset GM2 gangliosidoses are neurological disorders caused by marked deficiency of the A isoenzyme of beta-hexosaminidase; they occur in the Ashkenazi Jewish population, though less frequently than classic (infantile) Tay-Sachs disease. Earlier biosynthetic studies had identified a defective alpha-subunit that failed to associate with the beta-subunit. We have now found a guanosine to adenosine transition at the 3' end of exon 7, which causes substitution of serine for glycine at position 269 of the alpha-subunit [designated 269 (Gly----Ser) substitution]. An RNase protection assay was used to localize the mutation to a segment of mRNA from fibroblasts of a patient with the adult-onset disorder. That segment of mRNA (after reverse transcription) and a corresponding segment of genomic DNA were amplified by the polymerase chain reaction and sequenced by the dideoxy method. The sequence analysis, together with an assay based on the loss of a ScrFI restriction site, showed that the patient was a compound heterozygote who had inherited the 269 (Gly----Ser) mutation from his father and an allelic null mutation from his mother. The 269 (Gly----Ser) mutation, in compound heterozygosity with a presumed null allele, was also found in fetal fibroblasts with an association-defective phenotype and in cells from five patients with chronic GM2 gangliosidosis. It was not found in beta-hexosaminidase A-deficient cells obtained from patients with infantile Tay-Sachs disease nor in cells from individuals who do not have beta-hexosaminidase A deficiency. However, there must be additional mutations with similar consequences, since the 269 (Gly----Ser) substitution was not present in fibroblasts from two patients with juvenile GM2 gangliosidosis even though these had an association-defective alpha-subunit.<\/jats:p>","DOI":"10.1073\/pnas.86.7.2413","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:15:35Z","timestamp":1149059735000},"page":"2413-2417","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":62,"title":["Molecular basis of adult-onset and chronic GM2 gangliosidoses in patients of Ashkenazi Jewish origin: substitution of serine for glycine at position 269 of the alpha-subunit of beta-hexosaminidase."],"prefix":"10.1073","volume":"86","author":[{"given":"B H","family":"Paw","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, School of Medicine, University of California, Los Angeles 90024."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M M","family":"Kaback","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, School of Medicine, University of California, Los Angeles 90024."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E F","family":"Neufeld","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, School of Medicine, University of California, Los Angeles 90024."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1989,4]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.86.7.2413","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T12:54:35Z","timestamp":1649854475000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.86.7.2413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,4]]},"references-count":0,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1989,4]]}},"alternative-id":["10.1073\/pnas.86.7.2413"],"URL":"https:\/\/doi.org\/10.1073\/pnas.86.7.2413","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1989,4]]},"assertion":[{"value":"1989-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}