限制型心肌病患儿致病基因检测1例报告

Pathogenic gene detection in restrictive cardiomyopathy:a case report

目的分析TNNI3基因变异致可疑限制型心肌病的临床表型及基因型。方法回顾分析1例可疑限制型心肌病患儿的临床资料。结果患儿为4岁8月龄女孩,因咳嗽、发热,心电图异常入院。患儿心电图示双心房负荷重,左心室高电压;超声心动图示全心扩大,室壁运动减弱;心功能不全;少量心包积液;二尖瓣关闭不全(中量反流);肺动脉高压。患儿于入院2个月前曾有上楼时口唇发绀史。基因检测提示患儿存在TNNI 3基因c.575G>A杂合变异,其父母未携带该变异,属于新发变异。该变异使TNNI 3基因192位的精氨酸被组氨酸取代。多物种对比发现该位点具有高度保守性。各种预测软件提示该变异为有害变异。结论TNNI3基因c.575G>A(p.Arg192His)杂合变异很可能是本例患儿的致病变异。

Objective To explore the clinical phenotype and genotype of suspected restrictive cardiomyopathy caused by TNNI3 gene mutation.Method The clinical data from a child suspected of restrictive cardiomyopathy were retrospectively analyzed.Results A 4-year-8-month-old girl was admitted to hospital due to cough,fever and abnormal electrocardiogram.The electrocardiogram showed heavy load in both atria and high left ventricle voltage.Echocardiography showed whole heart enlargement with weakened motion,cardiac insufficiency,pericardial effusion(small amount),mitral regurgitation(moderate reflux)and pulmonary hypertension.Two months before admission,the child had a history of cyanosis when he went upstairs.Genetic test indicated that the child had a heterozygous mutation of c.575 G>A which was a new mutation in TNNI3 gene,and her parents did not carry the mutation.This mutation caused the arginine at position 192 of the TNNI3 to be replaced by histidine.Multi-species comparison found that this site was highly conserved.Various prediction softwares suggested that the mutation was deleterious.Conclusion The heterozygous mutation of c.575 G>A(p.Arg 192 His)in TNNI3 gene was likely to be the pathogenic mutation of the child.