title: Identification of two novel missense mutations (p.R1221C and p.R1357W) in the ABCC6 (MRP6) gene in a Japanese patient with pseudoxanthoma elasticum (PXE).
abstract: Pseudoxanthoma elasticum (PXE) is a rare, inherited, systemic disease of elastic tissue that in particular affects the skin, eyes, and cardiovascular system. Recently, the ABCC6 (MRP6) gene was found to cause PXE. A defective type of ABCC6 gene (16pl3.1) was determined in two Japanese patients with PXE. In order to determine whether these patients have a defect in ABCC6 gene, we examined each of 31 exons and flanking intron sequences by PCR methods (SSCP screening and direct sequencing). We found two novel missense variants in exon 26 and 29 in a compound heterozygous state in the first patient. One is a missense mutation (c.3661C>T; p.R1221C) in exon 26 and the other is a missense mutation (c.4069C>T; p.R1357W) in exon 29. These mutations have not been detected in our control panel of 200 alleles. To our knowledge, this is the first report of mutation identification in the ABCC6 gene in Japanese PXE patients. The second patient was homozygous for 2542_2543delG in ABCC6 gene and heterozygous for 6 kb deletion of LDL-R gene. This case is the first report of a genetically confirmed case of double mutations both in PXE and FH loci.
authors.affiliation: Molecular Genetics of Cardiovascular Disorders, Division of Cardiovascular Medicine (The Second Department of Internal Medicine), Graduate School of Medical Science, Kanazawa University, Kanazawa.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Noji
authors.forename: Akihiro
authors.initials: A
authors.lastname: Inazu
authors.forename: Toshinori
authors.initials: T
authors.lastname: Higashikata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nohara
authors.forename: Masa-aki
authors.initials: MA
authors.lastname: Kawashiri
authors.forename: Wenxin
authors.initials: W
authors.lastname: Yu
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Todo
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nozue
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Uno
authors.forename: Senshu
authors.initials: S
authors.lastname: Hifumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007564:Japan; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D011561:Pseudoxanthoma Elasticum / Q000235:genetics*
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human