TNNI3基因突变致儿童扩张型心肌病1例并文献复习

Dilated Cardiomyopathy Caused by TNNI3 Gene Mutation in Children:a Case Report

目的报告1个罕见的扩张型心肌病(DCM)致病基因突变位点,探讨其基因型与临床表型的关系.方法对1例TNNI3基因突变致DCM患儿的临床资料进行回顾性分析,采集患儿及其父母外周血基因组DNA,进行全外显子测序.对DCM相关文献进行复习.结果患儿,女,1岁零6个月起病,急性期主要表现为纳差、精神萎靡伴少尿,活动量少.心脏彩超提示左心室、左心房明显扩大,左室射血分数33%,左室缩短率16%,临床诊断为DCM,无阳性家族史.核心家系全外显子测序结果显示,患儿在TNNI3基因存在c.465 G>A(p.Met155Ile)杂合错义突变,且为新生突变,其父母均不携带该突变.目前仅2例肥厚型心肌病报道过该突变.结论TNNI3基因的c.465 G>A(p.Met155Ile)突变为DCM的可能致病突变,可能产生进行性的心衰表型.

Objective To report a rare gene mutation site in dilated cardiomyopathy(DCM),and to investigate the relationship between its genotype and clinical phenotype.Methods Clinical data of a child with DCM caused by TNNI3 gene mutation were retrospectively analyzed.The peripheral blood was collected from the child and her parents,and the genomic DNA was extracted for whole exon sequencing.Literatures relavant to DCM were collected and reviewed.Results The girl with onset at the age of 1-year and 6-month old mainly presented anorexia,fatigue,oliguria and hypoactivity.The color Doppler ultrasound showed the left ventricle and atrium enlargement with a left ventricular ejection fraction of 33%and a left ventricular shortening rate of 16%.The child was clinically diagnosed with DCM and had no positive family history.The trio-whole exome sequencing results showed that she had a de novo heterozygous missense variant c.465G>A(p.Met155Ile)in TNNI3 gene since neither of her parents carried the mutation.This variant has been reported in only 2 cases of hypertrophic cardiomyopathy.Conclusion The variant c.465G>A(p.Met155Ile)in TNNI3 gene may be a pathogenic mutation for DCM,which may result in a progressive heart failure phenotype.