title: Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum.
abstract: Pseudoxanthoma elasticum (PXE) is a hereditary disease, causing calcification and degeneration of elastic fibers, which affects the skin, eye, cardiovascular systems and gastrointestinal tract. PXE is caused by mutations in the ABCC6 gene. Neither detailed nor large-scale analyses have been accomplished in Japanese patients with PXE. We, therefore, investigated clinical symptoms and ABCC6 gene mutations in 76 Japanese patients. Japanese PXE patients (n = 76) had a significantly lower incidence of vascular lesions than 505 PXE patients in the Leiden Open Variation Database (LOVD) (38.7% vs 65.1%, respectively; P = 1.34E-06); however, the incidences of the skin, eye, cardiac and gastrointestinal lesion symptoms were not significantly different. Symptom severity scores for skin, eye and vascular lesions, calculated using the Phenodex™ system, were significantly lower in Japanese PXE patients than in LOVD PXE patients. Genetic analysis revealed three nonsense, four frame-shift, one exon deletion and 13 missense mutations in ABCC6 in 73 patients; however, we were unable to detect pathogenic mutations in three patients. Frequent mutations differed between Japanese and LOVD PXE patients. In Japanese PXE patients, the top five mutations accounted for more than 60% of all pathogenic changes, suggesting the presence of founder effects. Consistent with previous reports, no obvious correlations between genotypes and phenotypes were identified in this study. In conclusion, we consider that the milder clinical phenotypes, observed even in older Japanese PXE patients, could be attributed to environmental factors such as dietary habits and lifestyle, as well as genetic background.
authors.affiliation: Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Iwanaga
authors.affiliation: Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Okubo
authors.affiliation: Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Yozaki
authors.affiliation: Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Koike
authors.affiliation: Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kuwatsuka
authors.affiliation: Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Tomimura
authors.affiliation: Department of Healthcare Epidemiology Research, Graduate School of Medicine, Kyoto University, Kyoto, Japan.|Department of Dermatology, Graduate School of Biomedical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.|Division of Medical Information Technology and Administration Planning, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamura
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Maemura
authors.affiliation: Department of Ophthalmology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Tsuiki
authors.affiliation: Department of Ophthalmology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitaoka
authors.affiliation: Department of Dermatology, Graduate School of Biomedical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Human Genetics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mishima
authors.affiliation: Department of Human Genetics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Koh-Ichiro
authors.initials: KI
authors.lastname: Yoshiura
authors.affiliation: Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Aichi, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Ogi
authors.affiliation: Department of Dermatology, Osaka Medical College, Osaka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tanizaki
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Wataya-Kaneda
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Gunma University, Gunma, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Utani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D011561:Pseudoxanthoma Elasticum / Q000453:epidemiology / Q000235:genetics*; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human
keywords: 
  ABCC6
  ; angioid streak; cardiovascular disease; gene mutation; pseudoxanthoma elasticum