DSP复合杂合基因突变与扩张型心肌病的发生有关

目的:通过全外显子测序寻找扩张型心肌病(dilated cardiomyopathy,DCM)家系的致病基因,分析临床特点及基因突变位点。方法:收集在本院就诊的1例DCM患儿的临床资料,采集患儿及其父母的外周血,抽提血液DNA,进行全外显子测序,寻找致病基因,Sanger测序验证可能的致病基因突变,对其临床特点、实验室检查、基因突变进行综合分析。结果:将测序结果比对分析,多个生物数据库筛选、过滤,发现桥粒斑蛋白(desmoplakin,DSP)基因c.939+1G>A和c.4198C>T位点发生突变。DSP可能是该家系DCM的致病基因,并且DSP基因第1400位精氨酸残基在不同物种之间具有高度保守性。患儿左心房、左心室显著增大,左心室收缩功能减低(左心室射血分数为15%,左心室缩短分数为7%)。心电图提示窦性心动过速、心房肥大、T波改变(Ⅰ、V6导联T波倒置)。结论:DSP基因复合杂合突变(c.939+1G>A和c.4198C>T)与DCM紧密相关。分析临床特点与基因突变,对临床诊断心肌病提供依据。

Compound heterozygous DSP gene mutations c.939+1G>A and c.4198C>T are dilated cardiomyopathy related

Objective To search for the pathogenic gene mutations associated with dilated cardiomyopathy(DCM).Methods A four-year-old boy was found to have significantly enlarged left atrium and ventricle by echocardiography.The diagnosis of DCM was established and the clinical data of the proband and his relatives of a DCM pedigree were acquired.The DNA extracted from peripheral blood cells of all investigated subjects was subjected whole exome sequencing(WES).The Sanger sequencing was performed to verify findings form WES.Results With reference to the unaffected individuals and biological databases,compound heterozygous mutations of desmoplakin(DSP)gene,c.939+1 G>A and c.4198 C>T,were identified.The c.939+1 G>A led to reading frame shift and c.4198 C>T predicted a missense mutation af-fecing strictly conserved amino acid residue Arg 1400,p.Arg1400 val.The ventricular function decreased significantly with only 15%of left heart ejection fraction and 7%of left heart shortening score.Electrocardiogram revealed sinus tachy-cardia,atrial hypertrophy and T wave change.Conclusions The compound heterozygous mutation,c.939+1 G>A and c.4198 C>T,of DSP gene are associated with DCM,and further functional studies are warranted to clarify the molecular pathogenesis of the mutations.