title: Point mutations in the upstream region of the alpha-galactosidase A gene exon 6 in an atypical variant of Fabry disease.
abstract: Single point mutations in the upstream region of exon 6 of the alpha-galactosidase A gene were found in two Japanese cases of the cardiac form of Fabry disease; 301Arg----Gln (902G----A) in a case that has already been published and 279Gln----Glu (835C----G) in a new case. They both expressed markedly low, but significant, amounts of residual activity in COS-1 cells. In contrast, two unrelated cases with classic Fabry disease were found to have different point mutations, which showed a complete loss of enzyme activity in a transient expression assay; 328Gly----Arg (982G----A) in the downstream region of exon 6 in one case and two combined mutations, 66Glu----Gln (196G----C)/112Arg----Cys (334C----T), in exon 2 in the other. We conclude, on the basis of the results recorded in this study and those in previous reports, that the pathogenesis of atypical Fabry disease is closely associated with point mutations in the upstream region of exon 6 of the alpha-galactosidase A gene.
authors.affiliation: Department of Clinical Genetics, Tokyo Metropolitan Institute of Medical Sciences, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ishii
authors.forename: H
authors.initials: H
authors.lastname: Sakuraba
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D005091:Exons / Q000235:genetics; D000795:Fabry Disease / Q000201:enzymology* / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D000519:alpha-Galactosidase / Q000235:genetics* / Q000378:metabolism
chemical_list: D000519:alpha-Galactosidase