LMNA基因C.1583 C>G突变致Emery-Dreifuss型肌营养不良2个家系心脏受累特点研究  

Cardiac effects of the C.1583C>G LMNA mutation in two families with Emery-Dreifuss muscular dystrophy

作　　者：张丽[1] 张利宣[1] 张素华[1] 王静[1] 丁芳[1] 

机构地区：[1]河北医科大学第三医院干部病房,河北石家庄050051

出　　处：《河北医科大学学报》2016年第1期5-8,12,共5页Journal of Hebei Medical University

基　　金：河北省医学科学研究重点课题(20150274)

摘　　要：目的分析LMNA基因C.1583C>G突变致2个Emery-Dreifuss型肌营养不良(Emery-Dreifuss muscular dystrophy,EDMD)家系心脏受累特点。方法收集、分析2例先证者及其家系临床资料及血液标本(提取DNA),以及2例先证者活组织检查骨骼肌病理分析;PCR、直接测序;3例患者进行心电图、超声心动图、99 Tc MMIBI门控心肌灌注显像检查。结果家系1呈常染色体显性遗传,家系2为散发病例;3例患者均具有典型的EDMD临床表现:关节挛缩,进行性加重肌无力、肌萎缩,心律失常伴或不伴心肌病;活组织检查骨骼肌病理分析呈肌病改变;基因检测家系1(2例患者)、家系2(1例患者)LMNA基因9号外显子C.1583C>G(T528R)杂合错义突变;心电图及心脏影像学检查显示3例患者表现不同程度及类型的心律失常:窦性心动过速、心房扑动、Ⅲ度房室传导阻滞;家系2先证者合并心肌病,家系1先证者合并扩张型心肌病、心力衰竭;家系1先证者女儿无明显心脏结构功能异常。结论 2个家系3例患者经临床、活组织检查骨骼肌病理分析、基因检测确诊为EDMD,致病基因均为LMNA基因9号外显子C.1583C>G(T528R)杂合错义突变;LMNA基因突变所致EDMD心脏受累程度更严重,心脏传导系统受累常合并扩张型心肌病和(或)心力衰竭。Objective To report and analyze cardiac involvement in two Emery-Dreifuss muscular dystrophy（EDMD） pedigrees caused by C. 1583 C〉G mutation of the lamin A/C gene （LMNA）. Methods The characteristics of members of two families with EDMD were evaluated clinically, pathologically and genetically. Skeletal muscle biopsies and pathological analysis were performed in two probands. Electrocardiogram, ultrasound cardiography and 99TcM_MiBi_gated myocardiac perfusion imaging （99 TcM_MIBI GPI） were performed on three patients. Results Family history investigations revealed an autosomal dominant transmission pattern of disease in family 1, and a sporadic case in family 2. Three affected patients all presented typical clinical features of EDMD including joint contracture, muscle weakness, and cardiac involvement. Muscle histopathological study revealed dystrophic features. Moreover, each affected individual presented with cardiac arrhythmia, evident as sinus tachycardia, atrial flutter, or complete atrioventricular block. Cardiac imaging study showed dilated cardiomyopathy jn two patients,one of whom was undergoing heart failure, the second patient had no obvious abnormalities in cardiac structure or function. All three affected individuals had a heterozygous missense mutation in LMNA gene（C. 1583 C〉G） ,which caused a T528R amino acid change in LMNA protein. Conclusion Three patients were identified with EDMD, clinically, pathologically and genetically. Causative gene was missense mutation C. 1583 C〉G of LMNA. EDMD caused by mutation of LMNA presented more severe cardiac involvement, complicated with cardiac conduction system defect, cardiomyopathy and/or heart failure.

关 键 词：肌营养不良 Emery-Dreifuss型 心脏病 突变 

分 类 号：R746.2[医药卫生—神经病学与精神病学]