title: Alpha-galactosidase gene mutations in Fabry disease: heterogeneous expressions of mutant enzyme proteins.
abstract: Five point mutations were identified in unrelated Japanese Fabry disease hemizygotes: three new missense mutations, C142Y (425 G-->A), A156V (467 C-->T), and L166V (496 C-->G) in exon 3; one new splice site mutation at the 3' end of the consensus sequence in exon 4; one previously reported nonsense mutation, W44X (131 G-->A). C142Y expressed 50% of the normal enzyme protein in COS-1 cells, but catalytic activity was not detected. Both A156V and L166V expressed significant amounts of residual enzyme activity (6.7% and 9.8%) and enzyme proteins (10% each), the latter were more thermolabile at neutral pH than at acid pH, in vitro.
authors.affiliation: Department of Clinical Genetics, Tokyo Metropolitan Institute of Medical Science, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okumiya
authors.forename: S
authors.initials: S
authors.lastname: Ishii
authors.forename: R
authors.initials: R
authors.lastname: Kase
authors.forename: S
authors.initials: S
authors.lastname: Kamei
authors.forename: H
authors.initials: H
authors.lastname: Sakuraba
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002461:Cell Line, Transformed; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D004795:Enzyme Stability; D005091:Exons; D000795:Fabry Disease / Q000201:enzymology* / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D000519:alpha-Galactosidase / Q000737:chemistry / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004247:DNA; D000519:alpha-Galactosidase