1例以心脏受累为特点的DES基因突变鉴定及表型分析

Identification and Phenotypic Analysis of One Case of DES Gene Mutation Characterized by Cardiac Involvement

目的:分析1例以心脏受累为特点的DES基因突变病例的临床表型及突变位点。方法:收集1例在我院就诊并通过全外显子测序(WES)显示存在DES基因c.1360C>T突变,以严重心律失常、心肌病变为特点的患儿及其家系成员的临床资料。采集家系外周血,行Sanger测序鉴定可能致病的基因突变,通过生物信息学分析,预测突变的有害性。结果:Sanger测序验证了WES结果,患儿存在该位点杂合突变,但其父母不携带该突变,属于新发突变。突变使DES基因第454位的在不同物种间呈高度保守的精氨酸突变为色氨酸,预测软件提示该突变有害。通过表型分析,患儿存在双心房巨大,左室射血分数减低,接受了心脏永久起搏器植入。患儿心功能异常很可能是DES基因突变所致。该位点突变在中国属首次报道。结论:DES基因c.1360C>T突变很可能是患儿的致病突变。DES基因突变通常导致严重的心脏表型,病死率较高,预后较差。

Objective:To analyze the clinical phenotype and mutation site in a case of DES gene mutation characterized by cardiac involvement.Methods:The clinical data of a child with severe arrhythmia and cardiomyopathy and the family members were collected,the whole exome sequencing(WES)showed that there was a c.1360 C>T mutation in DES gene and was characterized by severe arrhythmia and cardiomyopathy.Peripheral blood of the family was collected and Sanger sequencing was performed to identify the possible pathogenic gene mutations,and the harmfulness of the mutations was predicted through bioinformatics analysis.Results:WES results were confirmed by Sanger sequencing.The child had heterozygous mutation at this site,but the parents did not carry the mutation,which was a de novo mutation.The mutation of DES 454 resulted in a highly conserved arginine mutation to tryptophan in different species,and the prediction software suggested that the mutation was harmful.Based on the analysis of phenotype,the child had large atria and reduced left ventricular ejection fraction,and then received permanent cardiac pacemaker implantation.The abnormal cardiac function was probably induced by the mutation of DES gene.This mutation was first reported in China.Conclusion:The mutation of DES c.1360 C>T is probably the pathogenic mutation of children.Mutations in DES gene usually lead to severe cardiac phenotype,higher fatality rate and poor prognosis.