title: A shortened beta-hexosaminidase alpha-chain in an Italian patient with infantile Tay-Sachs disease.
abstract: Fibroblasts derived from a beta-hexosaminidase A (HexA)-deficient infant with clinically classic Tay-Sachs disease synthesized a precursor alpha-chain that was smaller than its normal counterpart. Fibroblasts from the infant's parents, who were consanguinous, produced both normal and mutant alpha-chains. The size difference, estimated to be 2-3 kilodaltons on the basis of sodium dodecyl sulfate-polyacrylamide-gel electrophoresis, persisted after removal of oligosaccharides with endo-H and is therefore attributable to a shortened polypeptide. The mutant alpha-chain did not undergo the further posttranslational modifications characteristic of its normal counterpart--i.e., synthesis of the mannose phosphate recognition marker, association with the beta-chain to give HexA, and proteolytic conversion to the mature form. Nor was it secreted, even in the presence of NH4Cl. Instead, it disappeared in the course of a 20-h chase. These results suggest that the mutant alpha-chain was trapped in an early biosynthetic compartment, either the endoplasmic reticulum or the cis-Golgi. The mutation appears to be different from all those previously described in patients with clinically classic Tay-Sachs disease.
mesh_terms: D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005819:Genetic Markers; D054818:Hexosaminidase A; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D009154:Mutation; D013661:Tay-Sachs Disease / Q000201:enzymology / Q000235:genetics*; D001619:beta-N-Acetylhexosaminidases / Q000172:deficiency / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D007527:Isoenzymes; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases