核纤层蛋白A/C基因Glu82Lys突变与扩张型心肌病

Lamin A/C Gene Mutation Associated With Family Dilated Cardiomyopathy

目的 检测中国人家族性扩张型心肌病核纤层蛋白A/C(Lamin A/C)基因突变情况。方法对1个扩张型心肌病家系进行核纤层蛋白A/C、基因突变扫描,聚合酶链反应(PCR)扩增核纤层蛋白A/L’基因1～12号外显子,测序检测突变。对照为60例正常人及9例无明显家族史的扩张型心肌病伴传导阻滞病人。结果 该家系先证者第1号外显子PCR产物测序分析表明该患者核纤层蛋白A/C基因第82密码子位置发生G→A转换,使谷氨酸(Glu)变为赖氦酸(Lys)。该患者临床表现劳力性呼吸困难、心动过缓、胸闷、夜间不能平卧,超声示左心室扩大,心电图显示Ⅲ°房室传导阻滞,现已安装起搏器治疗。患者母亲及哥哥皆有相似临床症状且都已于40余岁心衰死亡,其家属有多人死于相同症状。结论 核纤层蛋白A/C基因Glu82Lys错义突变位于核纤层蛋白的杆状结陶域,有氨基酸的极性改变,该突变表型呈现症状重,发病早,预后差的临床特点,台并Ⅱ-Ⅲ°传导阻滞,提示该突变是致扩张型心肌病的恶性突变。

Objective To investigate the lamin A/C gene mutations in Chinese familial dilated cardiomyopathy. Methods One Chinese familie with dilated cardiomyopathy were chosen for the study. Exons 1～12 of the lamin A/C gene were sereened with both PCR （polymerase chain reaction） method and the cycle sequencing of the PCR products. Sixty normal controls and 9 cases of dilated cardiomyopathy accompany with atrioventricular block without any familial history mere as wnnols. Results A proband had a G to A transversion in the lamin A/C gene codon 82, resulted in the glutamic acid converted to lycine was found. The proband presented with symptoms of dyspnea, SB, heart failure. A two-dimensional echocardiogram showed left ventricular dysfunction （increased end-diastolic diameter）. ECG showed atrioventricular conduction system abnormalities （Ⅲ° AVB） and implanted pace maker. The proband＇s brother and one of his uncle had the similar clinical manifestions and both died of heart failure at the age of 40＇s. Fcur of his relatives died of the same symptom. Conclusion The missense mutation Glu82Lys lies in the rod domain of lamin A/C. It can change the polar of the amino acid. The affecfed member in this family showed a malignant phenotype of severe clinical symptoms, early onset, poor survival prognosis and atrioventricular conduction-system abnormalities （Ⅲ° AVB）, therefore, this mufaron is likely to be the disease-causing mutation of dilated cardiomyopathy.