Nakashima Mitsuko, Miyajima Masakazu, Sugano Hidenori, Iimura Yasushi, Kato Mitsuhiro, Tsurusaki Yoshinori, Miyake Noriko, Saitsu Hirotomo, Arai Hajime, Matsumoto Naomichi
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
J Hum Genet. 2014 Dec;59(12):691-3. doi: 10.1038/jhg.2014.95. Epub 2014 Nov 6.
Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by capillary malformation (port-wine stains), and choroidal and leptomeningeal vascular malformations. Previously, the recurrent somatic mutation c.548G>A (p.R183Q) in the G-α q gene (GNAQ) was identified as causative in SWS and non-syndromic port-wine stain patients using whole-genome sequencing. In this study, we investigated somatic mutations in GNAQ by next-generation sequencing. We first performed targeted amplicon sequencing of 15 blood-brain-paired samples in sporadic SWS and identified the recurrent somatic c.548G>A mutation in 80% of patients (12 of 15). The percentage of mutant alleles in brain tissues of these 12 patients ranged from 3.6 to 8.9%. We found no other somatic mutations in any of the seven GNAQ exons in the remaining three patients without c.548G>A. These findings suggest that the recurrent somatic GNAQ mutation c.548G>A is the major determinant genetic factor for SWS and imply that other mutated candidate gene(s) may exist in SWS.
斯特奇-韦伯综合征（SWS）是一种神经皮肤疾病，其特征为毛细血管畸形（葡萄酒色斑）以及脉络膜和软脑膜血管畸形。此前，利用全基因组测序在SWS和非综合征性葡萄酒色斑患者中，已鉴定出G-α q基因（GNAQ）中反复出现的体细胞突变c.548G>A（p.R183Q）是致病原因。在本研究中，我们通过二代测序研究了GNAQ中的体细胞突变。我们首先对散发性SWS的15对血脑样本进行了靶向扩增子测序，在80%的患者（15例中的12例）中鉴定出反复出现的体细胞c.548G>A突变。这12例患者脑组织中的突变等位基因百分比在3.6%至8.9%之间。在其余3例没有c.548G>A突变的患者中，我们在GNAQ的7个外显子中均未发现其他体细胞突变。这些发现表明，反复出现的体细胞GNAQ突变c.548G>A是SWS的主要决定性遗传因素，并暗示SWS中可能存在其他突变候选基因。
