title: Fabry disease: fourteen alpha-galactosidase A mutations in unrelated families from the United Kingdom and other European countries.
abstract: The nature of the molecular lesions in the alpha-galactosidase A gene causing Fabry disease in 12 unrelated families from the United Kingdom and 4 from other European countries was determined in order to provide precise heterozygote detection and prenatal diagnosis for these families. The entire alpha-galactosidase A coding region and flanking intronic sequences were analyzed by amplification of genomic DNA and solid-phase direct sequencing or by SSCP analysis followed by solid-phase direct sequencing. Fourteen new mutations were identified including 10 missense mutations (M42V, R49S, C56Y, D92H, D93G, P205T, W236C, W287G, N298H, and W340R), 2 nonsense mutations (Q107X and Q119X) and 2 small deletions (257del18 and 1087del1). Together with the previously reported mutations, a total of 33 lesions in the alpha-galactosidase A gene have been identified in unrelated British families, further documenting the molecular genetic heterogeneity of this disease.
authors.affiliation: Division of Biochemistry and Genetics, Institute of Child Health, University of London, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Davies
authors.forename: C M
authors.initials: CM
authors.lastname: Eng
authors.forename: J A
authors.initials: JA
authors.lastname: Hill
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: K
authors.initials: K
authors.lastname: MacDermot
authors.forename: B
authors.initials: B
authors.lastname: Winchester
authors.forename: R J
authors.initials: RJ
authors.lastname: Desnick
mesh_terms: D000795:Fabry Disease / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005858:Germany; D006579:Heterozygote; D006801:Humans; D007494:Ireland; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D017524:Slovenia; D006113:United Kingdom; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D000519:alpha-Galactosidase