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
Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Department of Healthcare Epidemiology Research, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
J Dermatol. 2017 Jun;44(6):644-650. doi: 10.1111/1346-8138.13727. Epub 2017 Feb 10.
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.
弹性假黄瘤（PXE）是一种遗传性疾病，可导致弹性纤维钙化和变性，影响皮肤、眼睛、心血管系统和胃肠道。PXE由ABCC6基因突变引起。此前尚未对日本PXE患者进行过详细或大规模分析。因此，我们对76例日本患者的临床症状和ABCC6基因突变进行了调查。日本PXE患者（n = 76）血管病变的发生率显著低于莱顿开放变异数据库（LOVD）中的505例PXE患者（分别为38.7%和65.1%；P = 1.34E - 06）；然而，皮肤、眼睛、心脏和胃肠道病变症状的发生率无显著差异。使用Phenodex™系统计算的日本PXE患者皮肤、眼睛和血管病变的症状严重程度评分显著低于LOVD PXE患者。基因分析显示，73例患者的ABCC6基因存在3个无义突变、4个移码突变、1个外显子缺失和13个错义突变；然而，我们在3例患者中未检测到致病突变。日本和LOVD PXE患者的常见突变有所不同。在日本PXE患者中，前五大突变占所有致病变化的60%以上，提示存在奠基者效应。与之前的报道一致，本研究未发现基因型与表型之间存在明显相关性。总之，我们认为，即使在老年日本PXE患者中观察到的较轻临床表型，可能归因于饮食习惯和生活方式等环境因素以及遗传背景。
