TTN及MYH7多基因突变与一家族性扩张型心肌病的相关性分析  

The relationship between multi-gene mutations of TTN and MYH7 and a Chinese familial dilated cardiomyopathy

作　　者：陈香璇 程维礼 张郁青[1] 何萍萍 余玉盛[2] 陶琴[1] CHEN Xiangxuan;CHENG Weili;ZHANG Yuqing;HE Pingping;YU Yusheng;TAO Qin(Department of Cardiology,Nanjing Jiangning Hospital,Nanjing,211100,China;Department of Medical Imaging,Nanjing Jiangning Hospital,Nanjing,211100,China)

机构地区：[1]南京市江宁医院心内科,南京211100 [2]南京市江宁医院医学影像科

出　　处：《临床心血管病杂志》2021年第8期744-748,共5页Journal of Clinical Cardiology

基　　金：南京市卫健委课题(No:YKK18204)。

摘　　要：目的:筛查一家族性扩张型心肌病(DCM)家系的致病基因,对其基因型与表型之间的关系进行分析。方法:研究对象为2017年南京市江宁医院收治的扩张型心肌病先证者及其家系成员共19例,另选取体检中心健康成年人50名作为对照。采集先证者及其家系成员的病史,并行超声心动图(UCG)和心脏磁共振(CMR)等检查,筛查出该家系其他3例扩张型心肌病患者。绘制家系图谱,使用二代测序法对先证者进行全基因组测序,筛选可疑致病基因。采用Sanger测序法进一步验证致病基因。结果:根据UCG及CMR结果,家系中除先证者(Ⅲ6)以外,其父亲(Ⅱ3)、伯父(Ⅱ1)、堂哥(Ⅲ2)等3人为扩张型心肌病患者。二代测序结果提示先证者携带TTN-E220 c.46467G>T(p.Glu15490Lys)、TTN-E102 c.28987 G>A(p.Ala 9663 Ser)、MYH7-E21 c.2420 G>A(p.Arg 807 His),Sanger测序进一步验证先证者携带以上3种基因突变。对家系中其他成员进行Sanger测序,结果示Ⅱ3、Ⅱ1、Ⅲ2均携带同样的3种基因突变。先证者、其父亲和堂哥均表现为胸闷症状,其伯父58岁猝死。未患病家系成员及健康对照人群中均未发现上述突变。结论:本研究发现该扩张型心肌病家系存在多基因突变,突变位点为TTN基因的双错义突变(p.Glu15490Lys、Ala 9663 Ser)及MYH7基因的单位点错义突变(p.Arg 807 His)。该家系中扩张型心肌病患者具有发病早的特点,且存在猝死患者,提示存在多基因突变的患者预后较差,但未发现持续性心律失常。Objective:To investigate the pathogenic genes of a familial dilated cardiomyopathy(FDCM)as well as the relationship between genotype and phenotype.Methods:The proband with DCM and his 19 family members in Nanjing Jiangning Hospital were enrolled.Fifty healthy adults in the same medical center were selected as controls.Data on medical history,ultrasonic cardiogram(UCG),and cardiac magnetic resonance(CMR)were obtained.The family tree was constructed.The whole genome of the proband was sequenced by next-generation sequencing technology and the suspected pathogenic genes were screened.Sanger sequencing technology was further used to verify the pathogenic genes.Results:According to the results of UCG and CMR,the proband’s father,his uncle,and one of his cousins were diagnosed as DCM.The results of next-generation sequencing showed that three mutant genes including TTN c.46467 G>T(p.Glu15490 Lys),TTN c.28987 G>A(Ala 9663 Ser),and MYH7 c.2420 G>A(p.Arg 807 His)were found in the proband,which was further proved by Sanger sequencing.Afterward,the same 3 mutation genes were found in the other three DCM patients in the family,while none of the mutations was found in the healthy controls and family members without DCM.The proband,his father and cousin all showed chest distress,and his uncle died suddenly at 58 years old.Conclusion:We find multi-gene mutations in the FDCM family,the mutation sites were double missense mutations of the TTN gene(p.Glu15490 Lys,Ala 9663 Ser)and unit missense mutation of the MYH7 gene(p.Arg 807 His).Patients with DCM in this family have the characteristics of early-onset and sudden death,which indicates that the prognosis of patients with multi-gene mutations is poor,but no persistent arrhythmia is found.

关 键 词：扩张型心肌病 基因突变 TTN MYH7 

分 类 号：R542.2[医药卫生—心血管疾病]