{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:24:48Z","timestamp":1776849888076,"version":"3.51.2"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[1991,12,16]],"date-time":"1991-12-16T00:00:00Z","timestamp":692841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[1991,12,16]],"date-time":"1991-12-16T00:00:00Z","timestamp":692841600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Neurosci"],"abstract":"<jats:p>Clinical phenotypes of GM2-gangliosidosis are complex. In the past 5 years it has become possible to dissect out the phenotypic complexity on the basis of abnormalities on the DNA level. Available data on the 18 disease-causing mutations so far identified in the P-hexosaminidase \u03b1-gene allow an oversimplified generalization; mutations that produce no or highly unstable mRNA cause the most severe infantile forms of the disease, while all late-onset forms are due to point mutations within the protein-coding region, which generate stable mRNA and stable mutant protein. The mutation underlying the distinct phenotype of Jewish adult Tay-Sachs disease will be discussed separately by Navon. The prototype of juvenile Tay-Sachs disease is the B1 variant. The disease was first recognized by an apparent discrepancy in the \u03b2-hexosaminidase activities toward the conventional artificial substrates and the natural lipid substrate, GM2-ganglioside. When assayed with the conventional artificial substrates, patients appear reasonably normal while they are severely deficient in hydrolysis of the natural substrate (and more recently the ''sulfated'' artificial substrate). The majority of B1 patients fall in the clinical category of juvenile GM2-gangliosidosis. Some of the earlier juvenile patients reported to have partial hexosaminidase A deficiency are likely to be B1 variant. Two point mutations, occurring at a mutation hot spot, CpG, and both affecting the same codon, have been described as the causes of the B1 variant phenotype; G533\u2192A, Arg178\u2192His; and C532\u2192T, Arg178\u2192Cys. The latter mutation has been found so far only in one Czechoslovakian family. In contrast, the former mutation has a wide geographic and ethnic distribution. While only 2 of the 3 patients we had studied earlier were homozygotes, 10 out of 11 patients from a relatively restricted region of Northern Portugal have turned out to be all homozygous with the same mutation. It is conceivable that this mutation originated in Northern Portugal. In contrast to the \u03b1-mutations, our knowledge in the \u03b2-subunit and the activator protein abnormalities is still limited. Only one specific mutation causing juvenile Sandhoff disease is known.<\/jats:p>","DOI":"10.1159\/000112175","type":"journal-article","created":{"date-parts":[[2007,11,30]],"date-time":"2007-11-30T09:43:15Z","timestamp":1196415795000},"page":"288-294","source":"Crossref","is-referenced-by-count":25,"title":["Biochemical and Molecular Aspects of Late-Onset GM2-Gangliosidosis: B1 Variant as a Prototype"],"prefix":"10.1159","author":[{"given":"Kunihiko","family":"Suzuki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie T.","family":"Vanier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[1991,12,16]]},"container-title":["Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/112175","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000112175","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T08:26:39Z","timestamp":1776846399000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000112175"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,12,16]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/000112175","archive":["Portico"],"relation":{},"ISSN":["0378-5866","1421-9859"],"issn-type":[{"value":"0378-5866","type":"print"},{"value":"1421-9859","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,12,16]]}}}