ACVRL1基因突变致合并主动脉窦瘤的遗传性出血性毛细血管扩张症1家系调查  

Hereditary hemorrhagic telangiectasia complicated by aortic sinus aneurysm caused by a pathogenic mutation in the ACVRL1 gene: a family survey

作　　者：闫娜[1] 刘燕[1] 李华军 李洋 谭宣丰 杨怡[5] 晋亮 Yan Na;Liu Yan;Li Huajun;Li Yang;Tan Xuanfeng;Yang Yi;Jin Liang(Department of Dermatology,Hanzhong Central Hospital,Hanzhong 723000,Shaanxi,China;Department of Cardiac Surgery,Hanzhong Central Hospital,Hanzhong 723000,Shaanxi,China;Department of Ultrasound Diagnosis,Hanzhong Central Hospital,Hanzhong 723000,Shaanxi,China;Department of Dermatology,The Second Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710004,China;Department of Dermatology,The First Medical Center of Chinese PLA General Hospital,Beijing 110853,China;Department of Dermatology,Air Force Medical Center,Beijing 110142,China)

机构地区：[1]汉中市中心医院皮肤科,汉中723000 [2]汉中市中心医院心脏外科,汉中723000 [3]汉中市中心医院超声诊断科,汉中723000 [4]西安交通大学第二附属医院皮肤科,西安710004 [5]解放军总医院第一医学中心皮肤科,北京110853 [6]空军特色医学中心皮肤科,北京110142

出　　处：《中华皮肤科杂志》2022年第8期716-720,共5页Chinese Journal of Dermatology

基　　金：空军军医大学"人才工程雏鹰计划"项目(KT2021HQ021)。

摘　　要：目的研究1个家族性合并主动脉窦瘤的遗传性出血性毛细血管扩张症家系的临床及遗传学特点,检测分析其致病基因。方法收集先证者及其亲属的临床资料和外周血,提取基因DNA,全外显子组测序筛查致病基因,随后采用Sanger测序验证。结果先证者及其女儿、外孙、外孙女ACVRL1基因在3号外显子137号核苷酸由鸟嘌呤G变为腺嘌呤A(c.137G>A),导致第46号氨基酸由半胱氨酸变为酪氨酸(p.C46Y),家系中另5例无临床症状者未携带此突变基因。结论该家系中合并主动脉窦瘤的遗传性出血性毛细血管扩张症Ⅱ型患者存在ACVRL1基因c.137G>A(p.C46Y)致病突变,亚洲人群未见此突变报道。Objective To investigate clinical and genetic characteristics of a family with hereditary hemorrhagic telangiectasia complicated by aortic sinus aneurysm,and to analyze causative genes.Methods Clinical data and peripheral blood samples were collected from the proband and her relatives,and genomic DNA was extracted.Causative genes were screened by whole-exome sequencing,and then verified by Sanger sequencing.Results A heterozygous mutation c.137G>A was identified at position 137 in exon 3 of the ACVRL1 gene in the proband,her daughter,grandson and granddaughter,which led to the substitution of cysteine by tyrosine at amino acid position 46(p.C46Y).The mutation was not found in any of the other 5 family members without clinical symptoms.Conclusion A causative mutation c.137G>A(p.C46Y)in the ACVRL1 gene was identified in the family with hereditary hemorrhagic telangiectasia type 2 complicated by aortic sinus aneurysm,which had not been previously reported in Asian populations.

关 键 词：毛细血管扩张 遗传性出血性 主动脉窦瘤 DNA突变分析 ACVRL1基因 

分 类 号：R543[医药卫生—心血管疾病]