散发性脑动静脉畸形中综合征基因的突变谱
Mutational spectrum of syndromic genes in sporadic brain arteriovenous malformation.
作者信息
Wang Kun, Zhang Mingqi, Zhao Sen, Xie Zhixin, Zhang Yisen, Liu Jian, Zhang Ying, Yang Xinjian, Wu Nan
机构信息
Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
出版信息
Chin Neurosurg J. 2022 Feb 24;8(1):4. doi: 10.1186/s41016-022-00270-8.
BACKGROUND
Brain arteriovenous malformations (BAVMs) are abnormal vessels that are apt to rupture, causing life-threatening intracranial hemorrhage (ICH). The estimated prevalence of BAVMs is 0.05% among otherwise healthy individuals. In this study, we aim to investigate the mutational spectrum of syndromic genes in sporadic BAVM.
METHODS
We recruited a cohort of 150 patients with BAVM and performed whole-exome sequencing on their peripheral blood DNA. To explore the mutational spectrum of syndromic genes in sporadic brain arteriovenous malformation, we selected six genes according to the Online Mendelian Inheritance in Man (OMIM) and literature. All variants in the six candidate genes were extracted and underwent filtering for qualifying variants.
RESULTS
There are a total of four patients with rare variants in hereditary hemorrhagic telangiectasia-related genes. In addition, we identified two patients have the variant of RASA1 gene in our database, which are also rare mutations that are absent from population databases. However, we did not find any patients with GNAQ mutations in our database.
CONCLUSIONS
In conclusion, we demonstrated that variants in syndromic vascular malformations play important roles in the etiology of sporadic BAVM.
背景
脑动静脉畸形（BAVMs）是易于破裂的异常血管，可导致危及生命的颅内出血（ICH）。在其他方面健康的个体中，BAVMs的估计患病率为0.05%。在本研究中，我们旨在调查散发性BAVM中综合征基因的突变谱。
方法
我们招募了150例BAVM患者队列，并对其外周血DNA进行全外显子测序。为了探索散发性脑动静脉畸形中综合征基因的突变谱，我们根据《人类孟德尔遗传在线》（OMIM）和文献选择了六个基因。提取六个候选基因中的所有变异，并对合格变异进行筛选。
结果
共有4例患者在遗传性出血性毛细血管扩张相关基因中存在罕见变异。此外，我们在数据库中鉴定出2例患者具有RASA1基因变异，这些也是人群数据库中不存在的罕见突变。然而，我们在数据库中未发现任何具有GNAQ突变的患者。
结论
总之，我们证明综合征性血管畸形中的变异在散发性BAVM的病因中起重要作用。
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