title: Molecular and clinical heterogeneity of adult GM2 gangliosidosis.
abstract: Adult GM2 gangliosidosis is a rare autosomal recessive disease with widely varying neurological and psychiatric manifestations. It is caused by marked deficiency, but not total absence, of beta-hexosaminidase (Hex) A, due to a single base change in the alpha-subunit gene of Hex, resulting in a substitution of Ser for Gly at position 269 in the alpha-subunit of the enzyme. The same mutation was identified in all investigated patients, most of whom are Ashkenazi Jews. Among previously studied non-Jewish patients of unrelated families this mutation appears either homozygously or in compound heterozygosity with an unidentified alpha-subunit mutation, whereas all Ashkenazi patients are compound heterozygotes. In all but one of them the other mutation is one of the Ashkenazi infantile Tay-Sachs alleles, while in one 76-year-old woman with very mild neurological symptoms, it is an unidentified alpha-subunit mutation. At present, the little correlation that seems to exist between these different genotypes and the severity of the disease poses a serious dilemma for genetic counselors.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Navon
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D004252:DNA Mutational Analysis; D015342:DNA Probes; D005260:Female; D005678:G(M2) Ganglioside / Q000378:metabolism*; D005733:Gangliosidoses / Q000145:classification / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D005796:Genes; D005808:Genes, Recessive; D005838:Genotype; D006579:Heterozygote; D054818:Hexosaminidase A; D006801:Humans; D007585:Jews; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000378:metabolism; D013661:Tay-Sachs Disease / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D015342:DNA Probes; D011498:Protein Precursors; D005678:G(M2) Ganglioside; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases