非综合征家族型主动脉夹层致病基因分析

Study on Pathogenic genes of non-syndromic familial aortic dissection

目的对非综合征家族型主动脉夹层家系成员进行分析,探索家系的致病基因及突变位点。方法筛查收集遂宁市中心医院和海军军医大学第一附属医院病案库里2008年10月至2020年7月诊断为“主动脉夹层”的非综合征家族型患者及其家系成员的血液及病例信息,通过对其血液样本的进行外显子获取和基因测序、生物信息学分析等实验步骤,总结非综合征家族型主动脉夹层的易感基因。结果总共筛查并收集了3个家系共48个成员的血液及临床信息,通过测序分析,在3个家系中发现了与非综合征家族型主动脉夹层最相关的2个突变基因的3个突变位点,分别为COL3A1基因突变c.2753G>A(p.G918E)、FBN1基因突变c.5678A>G(p.N1893S)、COL3A1基因突变c.1979G>T(p.G660V)。将所有的患者进行综合分析,发现了9个公有突变基因69个公有突变位点,其中ZNF806突变频率最高(36%)。结论FBN1、COL3A1为非综合征家族型主动脉夹层的易感基因,非综合征家族型主动脉夹层具有家族聚集性及遗传性,通过对该类核心家系的基因测序成为主动脉夹层易感基因筛查及致病机制研究的关键。

Objective To analyze members of families with non-syndromic familial aortic dissection and explore the pathogenic genes and mutation sites in these families.Methods The blood samples and medical records of the patients diagnosed with non-syndromic familial“aortic dissection”and their familial members from October 2008 to July 2020 were collected from the Suining Central Hospital and Shanghai Changhai Hospital.The exome capture,gene sequencing and bioinformatics analysis were performed on the blood samples to identify the susceptibility genes for non-syndromic familial aortic dissection.Results The blood samples and clinical information of 48 members from 3 families were screened and collected.Through sequencing analysis,3 mutational site in 2 mutant genes were found most associated with non-syndromic familial aortic dissection,i.e.,COL3A1 gene mutation c.2753G>A(p.G918E),FBN1 gene mutation c.5678A>G(p.N1893S)and COL3A1 gene mutation c.1979G>T(p.G660V).Based on a comprehensive analysis of all the patients,69 common mutational site in 9 common mutant genes were found,of which ZNF806 had the highest mutation frequency(36%).Conclusion FBN1 and COL3A1 would be the susceptibility genes of non-syndrome-family aortic dissection.Non-syndromic familial aortic dissection has familial aggregation and heredity.Gene sequencing of these nuclear families is the key to screen the susceptibility genes and study the pathogenic mechanism of aortic dissection.