回顾分析LMNA c.1045C>T突变所致核纤层蛋白病的临床表型  

Clinical Manifestations of Laminopathy Due to a Mutation in LMNA c.1045C>T

作　　者：芦阳 田庄 LU Yang;TIAN Zhuang(Department of Internal Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Department of Cardiology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Department of International medical service,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China)

机构地区：[1]北京协和医学院、中国医学科学院、北京协和医院内科,北京市100730 [2]北京协和医学院、中国医学科学院、北京协和医院心内科,北京市100730 [3]北京协和医学院、中国医学科学院、北京协和医院国际医疗部,北京市100730

出　　处：《中国分子心脏病学杂志》2022年第5期4916-4923,共8页Molecular Cardiology of China

基　　金：中央高水平医院临床科研业务费(2022-PUMCH-B-098);中国医学科学院医学与健康科技创新工程项目中国罕见病的精准诊疗研究(CIFMS#2021-I2M-1-003)。

摘　　要：目的对LMNA c.1045C>T突变所致核纤层蛋白病的临床表型进行汇总分析,提高对此种疾病的认识和诊治水平。方法结合北京协和医院诊治的1例LMNA c.1045C>T突变患者临床特点,总结文献收集的20例同一突变位点病例的临床资料并进行分析。结果LMNA c.1045C>T突变患者无性别差异,平均年龄32.9岁(14~46岁),临床表现为多系统受累,包括心肌病和/或心力衰竭(60%)、心律失常(60%,其中以传导异常为主)、脂肪萎缩(90%)、胰岛素抵抗或糖尿病(70%)、高甘油三酯血症(75%)、早发动脉粥样硬化(30%)和蛋白尿肾病(80%)。患者会出现相关心血管并发症,导致不良预后。其中3例发生心肌梗死,3例安装植入式心律转复除颤器(均为一级预防)。5例(25%)患者死亡或进行心脏移植,2例为猝死,另外2例分别死于感染性心内膜炎和感染后多脏器功能衰竭,1例因非缺血性心力衰竭进行心脏移植。针对上述患者出现的系统受累进行治疗有助于改善心力衰竭、胰岛素抵抗、血脂异常和血压,预防动脉粥样硬化和猝死的发生。结论LMNA c.1045C>T突变导致的核纤层蛋白病,具有明显的多系统受累临床特征,需要每年进行全身、代谢、心脏和肾脏等评估并进行治疗。未来需要从基因和发病机制层面进行深入研究和精准治疗。Objective To summarize and analyze the clinical phenotype of laminopathy caused by LMNA c.1045C>T mutation and in order to improve the understanding,diagnosis and treatment of the disease.Methods Based on the clinical characteristics of one patient with LMNA c.1045C>T mutation diagnosed and treated in our hospital,we summarized and analyzed the clinical data of 20 patients with the same mutation.Results There is no gender difference in the patients with LMNA c.1045C>T mutation.The average age is 32.9 years(14-46 years).The clinical manifestations included cardiomyopathy and/or heart failure(60%),arrhythmia(most of them were abnormal conduction),fat atrophy(90%),insulin resistance or diabetes(70%),hypertriglyceridemia(75%),premature atherosclerosis(30%)and proteinuria nephropathy(80%).These patients might develop cardiovascular complications resulting in a poor prognosis.Myocardial infarction occurred in 3 patients and implantable cardioverter-defibrillator(ICD)was implanted in 3 patients,all of which were primary prevention.5 patients(25%)died or underwent heart transplantation;2 patients died of sudden death,1 patient died of infective endocarditis and the other one died of post-infection multiple organ failure and 1 patient underwent heart transplantation because of non-ischemic heart failure.Systemic treatment can improve heart failure,insulin resistance,dyslipidemia and blood pressure,and prevent the occurrence and development of atherosclerosis and sudden death.Conclusion Laminopathy caused by LMNA c.1045C>T mutation has obvious clinical features of multi-system involvement,which needs to be annually evaluated about whole body,metabolism,heart and kidney.In the future,it is necessary to carry out profound researches on the level of gene and pathogenesis.

关 键 词：LMNA基因突变 核纤层蛋白病 心肌病 家族性部分脂肪萎缩 

分 类 号：R596[医药卫生—内科学]