两个汉族家族性扩张型心肌病家系致病基因与临床表型的相关研究  

Correlation between pathogenic genes and clinical phenotypes of two han families with familial dilated cardiomyopathy

作　　者：何萍萍 张郁青[1] 周宇 梁晴 陶琴[1] HE Pingping;ZHANG Yuqing;ZHOU Yu;LIANG Qing;TAO Qin(Department of Cardiology,Jiangning Hospital of Nanjing city,Nanjing 211100,China)

机构地区：[1]南京市江宁医院心血管内科,211100 [2]南京市江宁医院实验室,211100

出　　处：《心肺血管病杂志》2022年第2期190-196,共7页Journal of Cardiovascular and Pulmonary Diseases

基　　金：南京市卫健委课题(YKK20195);南京医科大学科技发展基金(NMUB 2021 0145)。

摘　　要：目的:通过对南京市江宁区两个汉族家族性扩张型心肌病(DCM)家系进行致病基因筛查,探讨家族性DCM的致病基因突变位点,并分析基因型与临床表型的关系。方法:对入选的2个患有家族性DCM的汉族家系的先证者及家系成员进行询问病史、家族史,并进行体格检查、常规心电图、超声心动图检查及3.0T心脏磁共振。同时为先证者及每个家系成员抽取5mL外周血,应用芯片捕获测序技术进行全基因组二代测序检测基因的突变情况,初步确定突变位点,对高通量测序中出现的疑似致病位点,均通过一代测序验证以最终确定突变位点。并对先证者及家系成员进行定期门诊和电话随访。另选取性别、年龄、种族与上述家系成员相匹配的健康人群120名作为对照。结果:其中一个家系(家系1)的先证者携带SCN5A-E6、TTN-E54、TTN-E43、TTN-E275两种基因的四种变异,3种预测软件预测这4种突变均为有害突变,而其弟弟、弟弟的儿子及孙女则均携带SCN5A-E6基因变异,且先证者及弟弟、弟弟的儿子均存在不同程度的心律失常;另一个家系(家系2)的先证者携带TTN-E288、DSP-E2两种基因的变异,3种预测软件预测这2种突变均为有害突变,而其父亲和儿子均携带TTN-E288基因的变异。两个家系的其余家系成员及120例健康对照人群均未检出上述基因变异位点。结论:两个家系中发现的基因突变位点目前国内外尚未有相关报道,其可能与我国汉族家族性DCM发病有关,且携带同一种致病基因的患者可能呈现相似的临床表型,携带多致病基因的患者临床症状较重,但其确切发病机制仍需进一步研究。Objective: by screening two families of dilated cardiomyopathy(DCM) in jiangning district, nanjing city, to investigate the pathogenic gene mutation sites of familial DCM and to analyze the relationship between genotype and clinical phenotype. Methods: the medical history and family history of the selected probands and family members of 2 han family members with familial dilated cardiomyopathy were inquired, and the physical examination, routine electrocardiogram, echocardiography and 3.0 T cardiac magnetic resonance were performed. At the same time, 5 mL of peripheral blood was extracted for the proband and each family member,and the whole genome second-generation sequencing was carried out by chip capture sequencing technology to detect the mutation status of genes, and the mutation sites were initially identified. The suspected pathogenic sites in high-throughput sequencing were verified by first-generation sequencing to determine the mutation sites.Regular outpatient visits and telephone follow-ups were conducted for the proband and family members.Another 120 healthy people whose sex, age and race were matched with the above family members were selected as controls. Results: in family 1, the progenitor carried four mutations that were SCN5 A-E6,TTN-E54,TTNE43 and TTN-E275 genes mutations, while the younger brother, the son and granddaughter of the younger brother all carried SCN5 A-E6 gene mutations, and the progenitor and the younger brother all had different degrees of arrhythmia.In another family,the proband carried TTN-E288 and DSP-E2 gene variants, while both the father and son carried TTN-E288 gene variants. The remaining members of the two families and 120 healthy controls did not detect the mutation sites. Conclusions: the gene mutation sites found in the two families may be related to the pathogenesis of dilated cardiomyopathy of the han nationality in China, and the patients with the same pathogenic gene may present similar clinical phenotype, and the more the pathogenic gene, the more severe the cl

关 键 词：心肌病 扩张型 致病基因 临床表型 

分 类 号：R54[医药卫生—心血管疾病]