肌球蛋白重链基因p.Gly743Arg和p.Glu1389Lys双突变致心脏疾病表型的研究  

Analyzing the clinical phenotype of heart disease caused by the double mutation of p.Gly743Arg and p.Glu1389Lys carrying the myosin heavy chain gene

作　　者：钟圣涵 王姚 陈维 韦江军 方庆华 龙湘林 何嘉程 邓松柏[1] 佘强[1] 杜建霖[1] Zhong Shenghan;Wang Yao;Chen Wei;Wei Jiangjun;Fang Qinghua;Long Xianglin;He Jiacheng;Deng Songbai;She Qiang;Du Jianlin(Department of Cardiovascular,the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China)

机构地区：[1]重庆医科大学附属第二医院心血管内科,重庆400010

出　　处：《中华危重病急救医学》2021年第11期1327-1331,共5页Chinese Critical Care Medicine

基　　金：重庆市自然科学基金(cstc2020jcyj-msxmX0210);重庆市科卫联合科研项目(2021MSXM217,2020FYYX047)。

摘　　要：目的探讨肌球蛋白重链基因(MYH6)p.Gly743Arg和p.Glu1389Lys双突变与心脏表型的关系。方法从2015至2020年就诊于重庆医科大学附属第二医院的52例无血缘关系的左心室肥厚(LVH)患者中筛选出携带MYH6基因p.Gly743Arg和p.Glu1389Lys双突变患者。二代全外显子测序检测技术对患者外周血进行基因检测,并对其家系成员基因组DNA进行Sanger测序验证。通过心电图、冠状动脉CT血管成像(CTA)、超声心动图、心脏磁共振成像(MRI)辅助检查手段,对患者心脏表型进行临床评估。结果52例无血缘关系的LVH患者进行了全外显子基因检测,其中1例(1.9%)MYH6基因p.Gly743Arg和p.Glu1389Lys双突变(先证者)。先证者母系成员中2位携带p.Glu1389Lys突变,但无明显临床表型;其父系成员中2位携带p.Gly743Arg突变,且有明显心动过缓临床表型,但无LVH。先证者男性,发病年龄21岁,表现为LVH伴窦性心动过缓,治疗前CTA未见冠状动脉狭窄,MRI提示左室舒张期末内径为58 mm。经血管紧张素受体-脑啡肽酶抑制剂(ARNI)治疗后,心电图提示心率明显增加(从43次/min增加到72次/min),超声心动图提示左室舒张期末内径明显缩小(从60 mm缩小到49 mm)。结论MYH6基因p.Glu1389Lys突变可以不表现为心脏疾病表型;MYH6基因p.Gly743Arg突变可以表现为无症状性窦性心动过缓,但无LVH表型;而MYH6基因p.Gly743Arg和p.Glu1389Lys双突变致心脏疾病表型较明显,青少年时期可出现无症状性LVH和窦性心动过缓表现,但经ARNI治疗可短期内逆转LVH表型。Objective To investigate the relationship between double mutations of myosin heavy chain gene(MYH6)p.Gly743Arg and p.Glu1389Lys and the cardiac phenotype.Methods Patients carrying double mutations in the MYH6 gene p.Gly743Arg and p.Glu1389Lys were screened from 52 unrelated left ventricular hypertrophy(LVH)who were admitted to the Second Hospital of Chongqing Medical University from 2015 to 2020,and the genetic testing of peripheral blood of patients by second-generation whole-exome sequencing assay technology and genomic DNA of their family members Sanger sequencing was performed to validate the genomic DNA of the family members.The cardiac phenotype was evaluated by electrocardiogram,coronary computed tomography angiography(CTA),echocardiography,and cardiac magnetic resonance imaging(MRI)as adjuncts.Results All whole-exome gene were detected in 52 unrelated patients with LVH,of which 1 patient(1.9%)had double mutations in MYH6 gene p.Gly743Arg and p.Glu1389Lys(proband).Two members of the maternal line of this patient carried p.Glu1389Lys mutation,but there was no obvious clinical phenotype.Two members of the paternal line carried p.Gly743Arg mutation and had obvious clinical phenotype of bradycardia,but there was no LVH.The male proband,aged 21 years old,presented with LVH and sinus bradycardia but no coronary artery stenosis on CTA before treatment,MRI showed that the left ventricular end diastolic diameter was 58 mm.After treatment with angiotensin receptor-enkephalinase inhibitor(ARNI),electrocardiogram showed that the heart rate increased significantly(from 43 bpm to 72 bpm).Echocardiography showed that the left ventricular end diastolic diameter decreased significantly(from 60 mm to 49 mm).Conclusions The p.Glu1389Lys mutation of the MYH6 gene may not manifest the phenotype of heart disease.MYH6 gene p.Gly743Arg mutation may be manifested asymptomatic sinus bradycardia,but there is no LVH phenotype.The cardiac disease phenotype caused by the double mutations of p.Gly743Arg and p.Glu1389Lys in the MYH6 gene

关 键 词：左心室肥厚 肌球蛋白重链 突变 临床表型 心源性猝死 血管紧张素受体-脑啡肽酶抑制剂 

分 类 号：R541.78[医药卫生—心血管疾病]