MYBPC3基因双突变肥厚型心肌病患者的临床表型分析  

Clinical Manifestations of Hypertrophic Cardiomyopathy Patients with Double Mutations in

作　　者：王静[1,2] 张梅[2] 吴桂鑫[3] 王继征[4] 宋雷[3,4] 邵一兵[1] WANG Jing;ZHANG Mei;WU Guixin;WANG Jizheng;SONG Lei;SHAO Yibing(Department of Cardiology,Qingdao Hospital,University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital),Qingdao 266071,Shandong,China;Department of Cardiology,Qilu Hospital of Shandong University,Jinan 250012,Shandong,China;Cardiomyopathy Ward,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100037,China;State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,National Center for Cardiovascular Disease,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100037,China)

机构地区：[1]康复大学青岛医院(青岛市市立医院)心内科,山东青岛266071 [2]山东大学齐鲁医院心内科,山东济南250012 [3]北京协和医学院,中国医学科学院,国家心血管病中心,阜外医院心肌病病区,北京100037 [4]中国医学科学院,北京协和医学院,国家心血管病中心阜外医院心,血管病国家重点实验室,北京100037

出　　处：《中国分子心脏病学杂志》2024年第4期6214-6219,共6页Molecular Cardiology of China

基　　金：黑龙江省“揭榜挂帅”科技攻关项目(2022ZXJ03C04)。

摘　　要：目的 明确携带MYBPC3基因双突变肥厚型心肌病(hypertrophic cardiomyopathy,HCM)患者的临床表型特点。方法 本研究纳入1999—2018年在中国医学科学院阜外医院就诊的HCM患者1 444例,行全外显子测序938例,行8个肌小节基因panel测序506例。检出的8个肌小节致病基因的变异按照美国遗传和基因组学会指南标准进行致病性分类,并按照患者携带变异的情况分为MYBPC3双突变组、其他肌小节基因双突变组、单突变组及无突变组。通过T载体克隆测序对部分存有心肌组织的MYBPC3双突变患者进行基因型分型。随访终点为心血管死亡。结果 遗传检测显示12例(0.8%)患者携带MYBPC3基因双突变,65例(4.5%)携带位于其他肌小节致病基因的双突变,583例(40.5%)携带单个突变,781例(54.2%)没有检测到肌小节基因突变。在(6.9±4.5)年随访期间,MYBPC3基因双突变患者发生心血管死亡的风险显著高于其他患者(Log rank P=1.19×10^(-10))。MYBPC3双突变患者中,4例经鉴定为反式复合突变患者,与其余MYBPC3基因双突变患者相比较,随访期内心血管死亡风险无差异(Log rank P=0.23)。结论 MYBPC3基因双突变HCM患者预后较差,应密切随访。Objective To clarify the clinical manifestations of hypertrophic cardiomyopathy(HCM) patients with double MYBPC3 gene mutations.Methods A total of 1 444 unrelated HCM probands were recruited,including 938 cases who underwent whole exome sequencing and 506 cases who underwent panel sequencing of 8 sarcomere genes.The variants located in 8 sarcomere genes detected in patients were classified according to the guidelines of the American Society of Genetics and Genomics.Patients were divided into MYBPC3 double mutation group,other double mutation group,single mutation group,and no mutation group based on the number of the variants.Genotyping of MYBPC3 double mutation patients were performed using T-vector cloning and sequencing.The primary endpoint was cardiovascular death.Results Twelve(0.8%) unrelated HCM patients were identified as carring double MYBPC3 mutations,65(4.5%) carried double mutations in other sarcomere genes,583(40.5%) carried single mutations,and 781(54.2%) had no sarcomere gene mutations.Over a(6.9±4.5) years follow-up period,patients with MYBPC3 double mutations were found to have a higher risk of cardiovascular death compared to other patients(Log rank P=1.19×10~(-10)).Among the MYBPC3 double patients,4 patients were identified as having trans-compound mutations,while the genotype of the remaining 8 patients remained uncertain.No significant difference was observed in the risk of cardiovascular death between patients with trans compound mutations and other MYBPC3 gene double mutations during the follow-up period(Log rank P=0.23).Conclusion HCM patients harboring double mutations inMYBPC3 gene show poor prognosis and should be followed closely.

关 键 词：肥厚型心肌病 MYBPC3基因 双突变 临床表型 

分 类 号：R542.2[医药卫生—心血管疾病]