title: A new mutation in the HEXA gene associated with a spinal muscular atrophy phenotype.
abstract: We describe two adult siblings who had had mild GM2 gangliosidosis since childhood. They presented with spinal muscular atrophy and dysarthria, and one sibling also had mental disturbances. Laboratory studies established the diagnosis of the B1 variant of GM2 gangliosidosis, because the hexosaminidase (Hex) A deficiency was not present upon testing with the unsulfated synthetic substrate 4-methylumbelliferyl N-acetylglucosaminide. HEXA gene analysis proved that the patients are compound heterozygotes for the previously identified G533-->A mutation and for a new mutation, G1171-->A, at exon 11. This new mutation affects a conserved amino acid and results in a Val-->Met substitution at position 391 of the HEXA gene. Full sequence of the alpha-subunit cDNA of Hex A revealed no other mutation. Assays for Hex A activities in patients suspected of having GM2 gangliosidosis should be performed with the sulfated substrate 4-methylumbelliferyl N-acetylglucosamine 6-sulfate.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Navon
authors.forename: R
authors.initials: R
authors.lastname: Khosravi
authors.forename: T
authors.initials: T
authors.lastname: Korczyn
authors.forename: M
authors.initials: M
authors.lastname: Masson
authors.forename: S
authors.initials: S
authors.lastname: Sonnino
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: B
authors.initials: B
authors.lastname: Eymard
authors.forename: M
authors.initials: M
authors.lastname: Lefevre
authors.forename: J C
authors.initials: JC
authors.lastname: Turpin
authors.forename: P
authors.initials: P
authors.lastname: Rondot
mesh_terms: D000328:Adult; D001483:Base Sequence; D005260:Female; D054818:Hexosaminidase A; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases