title: Novel mutations of ABCC6 gene in Japanese patients with Angioid streaks.
abstract: Angioid streaks (AS) are eye abnormalities caused by breaks in Bruch's membrane. The condition is often associated with pseudoxanthoma elasticum (PXE). The ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6) is reported to be the causal gene for PXE, although there have been no reports on whether the ABCC6 gene is the causal gene for AS. The aims of this study are to isolate the causal mutations for AS using a haplotype-based case-control study. We genotyped 54 Japanese AS patients and 150 controls for 5 single-nucleotide polymorphisms (SNPs). A simple association study using each SNP and a haplotype-based case-control study were performed. Twelve patients with special haplotypes for AS were selected, and were then subjected to gene sequencing. Six variants were successfully identified as causal mutations for AS (p.R419Q, p.E422K, c.2542delG, Del_Exon23, c.3774-3775insC and p.E1427K), and 4 of these were novel. This method can be applied to both identifying susceptibility variants of multifactorial diseases and isolating mutations in single-gene diseases.
authors.affiliation: Divisions of Molecular Diagnostics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mizutani
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Yuzawa
mesh_terms: D000328:Adult; D000368:Aged; D000793:Angioid Streaks / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods*; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human