一例马凡综合征家系患者的临床表现及遗传学分析  

Clinical Manifestation and Genetic Analysis of a Family With Marfan Syndrome

作　　者：孔志华 郭俊 王月丽[3] 李小燕 张晓萍[4] 陈丽 KONG Zhihua;GUO Jun;WANG Yueli;LI Xiaoyan;ZHANG Xiaoping;CHEN Li(Department of Ultrasound,Xianning Central Hospital,Xianning(437100),Hubei,China)

机构地区：[1]咸宁市中心医院超声医学科,湖北省437100 [2]国家儿童医学中心、首都医科大学附属北京儿童医院、北京市儿科研究所出生缺陷遗传学研究室、儿科重大疾病研究教育部重点实验室、出生缺陷遗传学研究北京市重点实验室 [3]首都医科大学附属北京安贞医院心脏超声医学中心 [4]北京市心肺血管疾病研究所心血管重塑相关疾病教育部重点实验室 [5]北京市心肺血管疾病研究所小儿心脏中心

出　　处：《中国循环杂志》2023年第2期189-194,共6页Chinese Circulation Journal

基　　金：国家自然科学基金(81770234)。

摘　　要：目的:通过对1例超声心动图表现为主动脉夹层、二尖瓣前叶脱垂并有主动脉夹层家族史的马凡综合征患者进行基因检测,明确其可能的致病变异基因,为临床诊断及遗传咨询提供理论依据。方法:对先证者行全外显子测序,利用生物信息学方法分析遗传性主动脉瘤相关基因,依据美国医学遗传学与基因组学学会(ACMG)指南鉴定候选致病突变;收集患者家系成员共计11人样本,利用Sanger测序对患者及家系成员的候选致病位点进行检测。结果:高通量测序结果提示患者携带原纤维蛋白1基因(FBN1)(NM_000138.5)c.7412delC杂合变异,位于60号外显子,Sanger测序结果表明该变异在家系内与疾病共分离。该位点为移码突变;依据ACMG指南,该变异为致病性变异[致病变异分类非常强(PVS1)+中等证据2(PM2)+辅助证据1(PP1)]。结论:该马凡综合征家系的致病原因为FBN1基因的c.7412delC突变,本研究为该家系的分子诊断、分子分型及后续遗传咨询及治疗选择提供了理论依据,丰富了中国马凡综合征患者FBN1基因的变异谱。Objectives:Whole exome sequencing was performed in a proband with Marfan phenotype including aortic root aneurysm and anterior mitral leaflet prolapse,to explore the possible genetic basis.Methods:Next-generation sequencing was used to identify the disease-causing mutation of the proband.The candidate pathogenic site was validated by Sanger sequencing in 11 family members,and the variant was analyzed according to the American College of Medical Genetics and Genomics(ACMG)2015 guidelines for variant interpretation.Results:Next-generation sequencing showed that there was an FBN1(NM_000138.5)frameshift mutation c.7412delC in the proband,which is in exon 60.Sanger sequencing results indicated that the variant was cosegregated in the family.According to ACMG guidelines,the mutation is a pathogenic variant(PVS1+PM2+PP1).Conclusions:The mutation of the FBN1 gene c.7412delC was the genetic cause of the Marfan syndrome in the family.The findings enrich the mutation spectrum of the FBN1 gene in the Chinese population.

关 键 词：马凡综合征 FBN1基因 临床表现 全外显子测序 

分 类 号：R54[医药卫生—心血管疾病]