RASA1 Mutations and Associated Phenotypes in 68 Families with Capillary Malformation-Arteriovenous Malformation
RASA1 Mutations and Associated Phenotypes in 68 Families with Capillary Malformation-Arteriovenous Malformation
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DOI：
10.1002/humu.22431
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发表时间：
2013-12-01
期刊：
影响因子：
3.9
通讯作者：
Vikkula, Miikka
中科院分区：
文献类型：
--
作者：
Revencu, Nicole;Boon, Laurence M.;Vikkula, Miikka
毛细血管畸形-动静脉畸形 (CM-AVM) 是一种常染色体显性遗传疾病，由 RASA1 杂合突变引起，表现为多灶性 CM 和快流病变的高风险。报道的患者数量有限，引发了表型边界的问题。我们确定了临床诊断为 CM-AVM 的新患者以及具有重叠表型的患者。 RASA1 在 261 名患有以下疾病的患者中进行了筛查：CM-AVM (n=100)、常见 CM（鲜红斑痣；n=100）、Sturge-Weber 综合征 (n=37) 或孤立性 AVM (n=24)。在 68 名 CM-AVM 指标患者中发现了 58 种不同的 RASA1 突变（其中 43 种是新突变），而在其他表型的患者中则没有发现这种突变。发现了一个新的临床特征：皮肤区域有许多小的白色淡晕，中央有一个红点。本研究解决的另一个问题是作为 CM-AVM 病理生理机制的二次打击假说。可获得来自具有种系 RASA1 突变的患者的一份组织。组织分析显示野生型 RASA1 等位基因缺失。总之，RASA1 突变强调了特定的 CM-AVM 表型，临床诊断基于识别特征性 CM。快流病变的高发生率需要仔细的临床和放射学检查以及定期随访。 (C) 2013 年 Wiley 期刊公司。
Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n=100), common CM(s) (port-wine stain; n=100), Sturge-Weber syndrome (n=37), or isolated AVM(s) (n=24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the second-hit hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up. (C) 2013 Wiley Periodicals, Inc.