全外显子组测序对肥厚型心肌病猝死者的基因分析

目的在全外显子组水平分析1例肥厚型心肌病(hypertrophic cardiomyopathy,HCM)猝死病例的相关致病性基因突变。方法对1例具有HCM病理学特征的猝死病例样本,利用Illumina~Hi Seq 2500平台进行全外显子组测序(whole exome sequencing,WES)。测序数据分析以hg19为参照序列,筛选可疑的单核苷酸变异位点,通过PhyloP、PolyPhen-2、SIFT等软件进行突变的保守性和功能分析。结果经过筛选,发现该病例的MYBPC3基因发生C719R杂合突变。结论利用二代测序技术进行全外显子组水平的分子解剖(基因突变检测和分析),有助于明确HCM的分子机制,并为死因分析提供新的方法和思路。

Gene Analysis for the Sudden Death of Hypertrophic Cardiomyopathy by Whole Exome Sequencing

Objective To analyze the related pathogenicity gene mutations in a sudden death of hypertrophic cardiomyopathy (HCM) on whole exome level.Methods Whole exome sequencing (WES) was been performed on a sudden death case sample with pathological features of HCM by Illumina(R) Hiseq 2500 platform.Using hgl9 as the reference sequences,the sequencing data were analyzed.Suspicious single nucleotide variants (SNV) were screened,and the conservatism and function were analyzed by the software such as PhyloP,PolyPhen-2,SIFT,etc.Results After screening,a heterozygous mutation C719R was finally identified in the gene MYBPC3 of this case.Conclusion The molecular anatomy on whole exome level by second generation sequencing technology can help to define the molecular mechanism of HCM and provide a new mothed and thought for analysis of death cause.