title: Identification of four novel mutations in five unrelated Korean families with Fabry disease.
abstract: Fabry disease is a X-linked recessively inherited metabolic disorder, which results from the deficient activity of the lysosomal hydrolase alpha-galactosidase A leading to the systemic deposition of glycosphingolipids with terminal alpha-galactosyl moieties. Single-strand conformation polymorphism (SSCP) analysis was performed, followed by DNA sequencing of PCR amplified exons of the human alpha-galactosidase A gene in 5 unrelated Korean patients with classic Fabry disease. Five different mutations were identified; two nonsense mutations (Y86X and R342X), one missense mutation (D266N), and two small deletions (296del2 and 802del4). Except for R342X mutation, four were novel mutations (Y86X, D266N, 296del2, 802del4). A T to G transversion at nucleotide position 5157 in exon 2 caused a tyrosine-to-stop substitution at codon 86. A G to A transition at position 10287 in exon 5 substituted an asparagine for an aspartate at codon 266. Mutation 296del2 in exon 2 resulted in a frame shift with a stop signal at the 22th codon downstream from the mutation, whereas mutation 802del4 resulted in a stop codon at the site of 4 bp deletion. In addition, the 802del4 was found to be a de novo mutation. This is the first report on mutation analysis of the human alpha-galactosidase A gene in Korean patients with Fabry disease.
authors.affiliation: Department of Neurology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.forename: G H
authors.initials: GH
authors.lastname: Kim
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.forename: K K
authors.initials: KK
authors.lastname: Kim
authors.forename: M C
authors.initials: MC
authors.lastname: Lee
authors.forename: H W
authors.initials: HW
authors.lastname: Yoo
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D018389:Codon, Nonsense / Q000235:genetics; D004252:DNA Mutational Analysis; D000795:Fabry Disease / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007723:Korea; D007962:Leukocytes / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics; D000519:alpha-Galactosidase / Q000737:chemistry / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D000519:alpha-Galactosidase