Expanding the clinical and molecular findings in RASA1 capillary malformation-arteriovenous malformation
Expanding the clinical and molecular findings in RASA1 capillary malformation-arteriovenous malformation
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扩展 RASA1 毛细血管畸形-动静脉畸形的临床和分子发现
DOI：
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发表时间：
2018
影响因子：
5.2
通讯作者：
P. Bayrak
中科院分区：
文献类型：
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作者：
Whitney L. Wooderchak;P. Johnson;J. McDonald;F. Blei;A. Berenstein;M. Sorscher;J. Mayer;A. Scheuerle;Tracey Lewis;J. F. Grimmer;G. Richter;Marcie A. Steeves;A. Lin;D. Stevenson;P. Bayrak
RASA 1相关疾病是以遗传性毛细血管畸形（CM）伴或不伴动静脉畸形（AVM）、动静脉瘘（AVF）或Parkes Weber综合征为特征的血管畸形综合征。报告的病例数量相对较少;虽然主要临床特征是CM和AVM/AVF，但RASA 1基因变异引起的更广泛表型谱仍在确定中。在这里，我们报告了69例在ARUP实验室鉴定的RASA 1变异的不相关病例的临床和分子学结果。桑格测序和多重连接依赖性探针扩增主要用于评估RASA 1。使用下一代测序（NGS）和阵列比较基因组杂交（aCGH）评估了几个非典型病例。60名个体具有有害的RASA 1变体，其中29名是新的。九个人有一个不确定的意义的变体。检测到5个大的RASA 1缺失，在阳性病例中总的缺失/重复率为8.3%（5/60）。大多数（75.4%）携带RASA 1变异的个体患有CM，44.9%患有AVM/AVF。在一些病例中的临床发现扩大了RASA 1表型。我们的数据表明，在这种疾病中筛查大的RASA 1缺失和重复是重要的，并表明NGS多基因面板测试有利于复杂血管表型病例的分子诊断。
RASA1-related disorders are vascular malformation syndromes characterized by hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM), arteriovenous fistulas (AVF), or Parkes Weber syndrome. The number of cases reported is relatively small; and while the main clinical features are CMs and AVMs/AVFs, the broader phenotypic spectrum caused by variants in the RASA1 gene is still being defined. Here, we report the clinical and molecular findings in 69 unrelated cases with a RASA1 variant identified at ARUP Laboratories. Sanger sequencing and multiplex ligation-dependent probe amplification were primarily used to evaluate RASA1. Several atypical cases were evaluated using next-generation sequencing (NGS) and array-comparative genomic hybridization (aCGH). Sixty individuals had a deleterious RASA1 variant of which 29 were novel. Nine individuals had a variant of uncertain significance. Five large RASA1 deletions were detected, giving an overall deletion/duplication rate of 8.3% (5/60) among positive cases. Most (75.4%) individuals with a RASA1 variant had CMs, and 44.9% had an AVM/AVF. Clinical findings in several cases expand the RASA1 phenotype. Our data suggest that screening for large RASA1 deletions and duplications in this disorder is important and suggest that NGS multi-gene panel testing is beneficial for the molecular diagnosis of cases with complex vascular phenotypes.
影响因子：
9.8
作者：
Ioannidis, Nilah M.;Rothstein, Joseph H.;Sieh, Weiva
通讯作者：
Sieh, Weiva