湖北地区一扩张型心肌病家系致病基因筛查

目的 对湖北地区一个扩张型心肌病家系成员进行致病候选基因筛查,寻求家族性扩张型心肌病致病基因,探讨基因型和表型关系.方法 先证者及其家族成员来自湖北省大冶市,先证者于2017年4月在武汉大学人民医院确诊为扩张型心肌病,已有家族成员死亡.详细询问先证者及其家属成员病史、家族史,并进行体格检查、血液指标、心脏超声和心电图检查.对患者的病史、家族史及检查结果分析.与先证者及其家属签订知情同意书,由武汉大学人民医院临床分子诊断中心对先证者候选致病基因全外显子高通量测序,获得可疑突变后,利用Sanger测序验证家系成员是否存在可疑突变.结果 家系先证者(Ⅲ3)和妹妹(Ⅲ2)携带肌联蛋白(TTN)c.100126A>G(P.Thr33376Ala)错义突变.先证者目前心功能下降并伴有恶性心律失常,而其妹妹无明显临床症状,心脏超声检查无异常.结论 本研究发现湖北地区一家族性扩张型心肌病家系存在TTN基因c.100126A>G(p.Thr33376Ala)错义突变,TTN与扩张型心肌病密切相关,是家族性扩张型心肌病重要致病基因.

Mutation screening for the causative gene in a dilated cardiomyopathy pedigree of Hubei province

Objective To screen the candidate pathogenic gene among family members of a dilated cardiomy-opathy (DCM), and find the relationship between the genotype and the phenotype. Methods The proband and family members came from Daye City, Hubei Province. The proband was diagnosed with dilated cardiomyopathy at Renmin Hospital of Wuhan University in April 2017, and some of his family member were dead then. The inheritance atlas was drawn, and analysis of genetic characteristics and clinical phenotype was performed. The candidated gene exon of the proband was sequenced by high-throughput sequencing, and ultimately the target area of the exon and mutations of can-didate genes were screened. Then bidirectional sequencing of Sanger was used to sequence other family members which were matching with gender and age to testify whether there are the above mutations. Results In this family, the proband and his sister carry one missense mutations, with TTN c.100126A>G (p.Thr33376Ala). The heart function of proband was declined and accompanied by malignant arrhythmia. But his sister has no obvious clinical symptoms. Conclusion The patient of this family carries the genetic mutation of TTN. TTN truncating mutations are a common cause of dilated cardiomyopathy, which maybe improve our understanding of the pathophysiology of dilated cardiomy-opathy.