title: Characterization of unusual hexosaminidase A (HEX A) deficient human mutants.
abstract: Two families with unusual hexosaminidase A (HEX A) mutations are described. In one, the proband had the Tay-Sachs disease phenotype with considerable HEX A activity. In the second, the proband was phenotypically normal with absent HEX A activity. Activities using ganglioside GM2 as substrate demonstrate markedly reduced activities in the first case and half-normal activities in the second. Pedigree analyses indicate the presence of two different mutations. In the first, the proband appears to be an allelic compound HEX A 2-4 where mutation HEX A 4 leads to a diminution of HEX A activity against GM2 but not for the synthetic substrate, 4MU-beta-D-N-acetyl-glucosaminide, with HEX A 2 being the Tay-Sachs disease (or similar) mutation. In the second family, the proband is an allelic compound HEX A 2-5 where mutation HEX A 5 leads to a diminution of HEX A activity against the synthetic substrate, 4MU-beta-D-N-acetyl-glucosaminide, but not for GM2. The presence of either mutation will lead to false-negative (HEX A 4) or false-positive (HEX A 5) assignments of heterozygosity or homozygosity for GM2 gangliosidosis when synthetic substrates are employed. In both families, DM2 N-acetyl-beta-D-galactosaminidase activity in fibroblasts was an accurate determinant of phenotype.
mesh_terms: D000328:Adult; D005260:Female; D005678:G(M2) Ganglioside / Q000378:metabolism; D006596:Hexosaminidases / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D012867:Skin / Q000201:enzymology; D013379:Substrate Specificity; D013661:Tay-Sachs Disease / Q000235:genetics
chemical_list: D005678:G(M2) Ganglioside; D006596:Hexosaminidases