Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum

Akira Iwanaga, Yumi Okubo, Mariko Yozaki, Yuta Koike, Yutaka Kuwatsuka, Saori Tomimura, Yosuke Yamamoto, Hiroshi Tamura, Satoshi Ikeda, Koji Maemura, Eiko Tsuiki, Takashi Kitaoka, Yuichiro Endo, Hiroyuki Mishima, Koh Ichiro Yoshiura, Tomoo Ogi, Hideaki Tanizaki, Mari Wataya-Kaneda, Tomoyasu Hattori, Atsushi Utani

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)644-650
Number of pages7
JournalJournal of Dermatology
Volume44
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

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Pseudoxanthoma Elasticum
Mutation
Databases
Skin
Blood Vessels
Founder Effect
Inborn Genetic Diseases
Elastic Tissue
Incidence
Genetic Association Studies
Feeding Behavior
Missense Mutation
Cardiovascular System
Genes
Gastrointestinal Tract
Life Style
Exons

All Science Journal Classification (ASJC) codes

  • Dermatology

Cite this

Iwanaga, A., Okubo, Y., Yozaki, M., Koike, Y., Kuwatsuka, Y., Tomimura, S., ... Utani, A. (2017). Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum. Journal of Dermatology, 44(6), 644-650. https://doi.org/10.1111/1346-8138.13727

Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum. / Iwanaga, Akira; Okubo, Yumi; Yozaki, Mariko; Koike, Yuta; Kuwatsuka, Yutaka; Tomimura, Saori; Yamamoto, Yosuke; Tamura, Hiroshi; Ikeda, Satoshi; Maemura, Koji; Tsuiki, Eiko; Kitaoka, Takashi; Endo, Yuichiro; Mishima, Hiroyuki; Yoshiura, Koh Ichiro; Ogi, Tomoo; Tanizaki, Hideaki; Wataya-Kaneda, Mari; Hattori, Tomoyasu; Utani, Atsushi.

In: Journal of Dermatology, Vol. 44, No. 6, 01.06.2017, p. 644-650.

Research output: Contribution to journalArticle

Iwanaga, A, Okubo, Y, Yozaki, M, Koike, Y, Kuwatsuka, Y, Tomimura, S, Yamamoto, Y, Tamura, H, Ikeda, S, Maemura, K, Tsuiki, E, Kitaoka, T, Endo, Y, Mishima, H, Yoshiura, KI, Ogi, T, Tanizaki, H, Wataya-Kaneda, M, Hattori, T & Utani, A 2017, 'Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum', Journal of Dermatology, vol. 44, no. 6, pp. 644-650. https://doi.org/10.1111/1346-8138.13727
Iwanaga, Akira ; Okubo, Yumi ; Yozaki, Mariko ; Koike, Yuta ; Kuwatsuka, Yutaka ; Tomimura, Saori ; Yamamoto, Yosuke ; Tamura, Hiroshi ; Ikeda, Satoshi ; Maemura, Koji ; Tsuiki, Eiko ; Kitaoka, Takashi ; Endo, Yuichiro ; Mishima, Hiroyuki ; Yoshiura, Koh Ichiro ; Ogi, Tomoo ; Tanizaki, Hideaki ; Wataya-Kaneda, Mari ; Hattori, Tomoyasu ; Utani, Atsushi. / Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum. In: Journal of Dermatology. 2017 ; Vol. 44, No. 6. pp. 644-650.
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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.",
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AU - Kuwatsuka, Yutaka

AU - Tomimura, Saori

AU - Yamamoto, Yosuke

AU - Tamura, Hiroshi

AU - Ikeda, Satoshi

AU - Maemura, Koji

AU - Tsuiki, Eiko

AU - Kitaoka, Takashi

AU - Endo, Yuichiro

AU - Mishima, Hiroyuki

AU - Yoshiura, Koh Ichiro

AU - Ogi, Tomoo

AU - Tanizaki, Hideaki

AU - Wataya-Kaneda, Mari

AU - Hattori, Tomoyasu

AU - Utani, Atsushi

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