核纤层蛋白基因c.16C>T突变所致家族性扩张型心肌病的临床和分子遗传学特征分析

Clinical and molecular genetic features of familial dilated cardiomyopathy caused by lamin A/C gene c.16C>T mutation

目的分析1例家族性扩张型心肌病(FDCM)患者及其家系成员的临床和分子遗传学特征。方法对2016年12月7日就诊于首都医科大学附属北京安贞医院的1例FDCM患者(女性,47岁;)的临床资料进行分析,包括病史、体格检查、心电图、影像学资料等,并进一步采集患者及其亲属的外周静脉血样,使用靶向外显子捕获测序方法对241种遗传性心肌病的相关致病基因进行测序,并进一步通过Sanger测序对可能突变的基因进行验证,分析其基因型与表现型的关系。结果先证者以心房颤动及窦房结功能障碍为首发表现,经由心电图、超声心动图及心脏磁共振成像检查确诊为扩张型心肌病。基因检测发现,该家系存在核纤层蛋白基因(LMNA基因)的c.16C>T(p.Q6X)突变。包括先证者共有6名家系成员携带该突变基因,其中4名携带者虽无心脏扩大征象但均合并不同程度的房室传导阻滞及房性心律失常,1名携带者的临床表现及辅助检查未见明显异常。结论 FDCM相关LMNA基因的c.16C>T突变外显率高,常以传导阻滞及房性心律失常作为该疾病的首发表现。

Objective To investigate clinical and molecular genetic features of a Chinese pedigree with familial dilated cardiomyopathy（FDCM）. Methods One 47 years old female patient with FDCM who was admitted at December 7th, 2016 in Beijing Anzhen Hospital, Capital Medical University and her family were included in this study. Clinical data including medical history, physical examination, electrocardiogram and echocardiogram findings were collected, and peripheral venous blood was sampled in all subjects for genetic testing. Two hundred and forty-one genes related to hereditary cardiomyopathy were detected by targeted exon-capture and sequencing technique, and candidate mutations were confirmed by the Sanger bi-directional sequencing. The genotype-phenotype correlation in this pedigree was analyzed. Results First manifestations of the proband were atrial fibrillation and sinus node dysfunction, and she was diagnosed with dilated cardiomyopathy by electrocardiogram, echocardiogram and cardiac magnetic resonance imaging. A c.16C〉T （p.Q6X） mutation of lamin A/C gene （LMNA） was identified, 6 individuals in this family were carriers, 4 of them had atrioventricular block and atrial arrhythmia without showing marked cardiac dilatation, 1 carrier showed no obvious abnormity in clinical manifestation and auxiliary examination. Conclusions Mutation of c.16C〉T in LMNA is related to FDCM and it has a high penetrance in the pedigree with FDCM. The disease is characterized by early performances of conduction defect and atrial arrhythmia.