2024 年第 8 期 第 0 卷

综合征型黏液样二尖瓣病变患者FBN1基因突变c.7819+1G>A及家系基因分析

FBN1 gene mutation c.7819+1G>A in a patient with syndromic myxoid mitral valve disease and genetic analysis of the family

作者：田白羽王坚刚韩杰焦玉清

英文作者：Tian Baiyu Wang Jiangang Han Jie Jiao Yuqing

单位：首都医科大学附属北京安贞医院瓣膜外科中心，北京100029

英文单位：Valve Surgery Center Beijing Anzhen Hospital Capital Medical University Beijing 100029 China

关键词：FBN1基因；黏液样二尖瓣病变；二尖瓣脱垂；马方综合征；全外显子测序

英文关键词：FBN1gene;Myxoidmitralvalvelesions;Mitralvalveprolapse;Marfansyndrome;Wholeexomesequencing

• 摘要：

• 目的 探讨1例黏液样二尖瓣病变患者及家系的致病基因及突变位点。方法 根据首都医科大学附属北京安贞医院瓣膜外科中心1例既往因黏液样二尖瓣病变就诊的二尖瓣关闭不全患者的全外显子检测结果，对患者家系中双亲、兄长、双胞胎妹妹进行抽血化验。抽取外周静脉血，提取家系成员基因组DNA，采用高通量测序平台对先证者其父母兄妹4人进行全外显子组测序。对可疑突变扩展至家系成员进行Sanger测序验证。结果 测序结果发现先证者和其妹妹FBN1基因第63外显子和63内含子交界处出现c.7819+1G>A剪接变异。该变异为新发突变，且为致病突变。该家系中黏液样二尖瓣病变为综合征型。结论 第15号染色体FBN1基因(NM000138.4)为致病基因。第63外显子和63内含子交界处出现的c.7819+1G>A剪接变异为国内首次，全球第3次报道，为日后的基因筛查及治疗提供一定依据。

• Objective To explore the pathogenic gene and mutation site of a patient with myxoid mitral valve disease and the family. Methods  According to the results of whole exome sequencing in a patient with mitral regurgitation who had been admitted to the Valve Surgery Center, Beijing Anzhen Hospital, Capital Medical University due to myxoid mitral valve disease, blood samples were taken from the parents, brother and twin sister of the patient′s family. Peripheral venous blood was collected to extract genomic DNA from the family members. Whole exome sequencing was performed on the proband′s parents and siblings using a high-throughput sequencing platform. Suspected mutations were verified by Sanger sequencing in family members. Results  Sequencing results showed that the proband and his sister had c.7819+1G>A splice variant at the junction of exon 63 and intron 63 of the FBN1 gene. This mutation was a novel and pathogenic mutation. The myxoid mitral valve lesions in this family were syndromic. Conclusions  FBN1 gene (NM000138.4) on chromosome 15 is the pathogenic gene. The c.7819+1G>A splice variant at the junction of exon 63 and intron 63 is reported for the first time in China and the third time in the world, which provides a basis for gene screening and treatment in the future.