MYBPC3和MYH7双变异致左心室致密化不全患者的临床表型及基因变异分析  

Clinical phenotype and genetic analysis of patients with left ventricular noncompaction caused by the biallelic mutation of MYBPC3 and MYH7

作　　者：张亚辉 李小燕[2] 宋邦荣[3] 王月丽[4] 张峻瑞 任燕龙[6] Zhang Yahui;Li Xiaoyan;Song Bangrong;Wang Yueli;Zhang Junrui;Ren Yanlong(Department of Acute Coronary Syndrome Ward,Center for Coronary Artery Disesse,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China;Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart Lung and Blood Vessel Diseases,Key Laboratory of Remodeling-Related Cardiovascular Disease of the Ministry of Education,Beijing 100029,China;Department of Cardiac Surgery,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China;Department of Echocardiography,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China;Department of Cardiology,Shanxi Cardiovascular Hospital,Taiyuan 030024,China;Intensive Care Unit,Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University,Beijing Engineering Research Center of Cardiovascular Wisdom Diagnosis and Treatment,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院冠心病中心急诊冠脉病区,北京100029 [2]首都医科大学附属北京安贞医院、北京市心肺血管疾病研究所心血管重塑相关疾病教育部重点实验室,北京100029 [3]首都医科大学附属北京安贞医院心外科,北京100029 [4]首都医科大学附属北京安贞医院超声心动科,北京100029 [5]山西省心血管病医院心血管内科,太原030024 [6]首都医科大学附属北京安贞医院心内科重症监护室,心血管智慧诊疗北京市工程研究中心,北京100029

出　　处：《中华心血管病杂志》2023年第11期1160-1165,共6页Chinese Journal of Cardiology

基　　金：北京市属医院科研培育计划(PZ2021007);北京市医院管理中心青年人才培养“青苗”计划(QML20200604)。

摘　　要：目的探讨左心室致密化不全(LVNC)家系携带的致病基因及致病突变与临床表型的关系。方法研究对象为1例LVNC患者及其家系成员。收集先证者及其家系成员的病史、12导联心电图、超声心动图及心脏磁共振检查结果。对先证者行全外显子测序,重点对与遗传性心肌病相关基因进行分析,应用Sanger测序对候选致病位点进行验证。依据美国医学遗传学与基因组学学会指南进行致病性判定。结果先证者携带MYBPC3基因c.C2827T无义变异和MYH7基因c.G2221C错义变异。先证者姐姐携带MYBPC3基因c.C2827T无义变异。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南对变异位点进行致病性判定,均为有害变异。结论MYBPC3基因c.C2827T和MYH7基因c.G2221C杂合变异是先证者心肌致密化不全的致病原因,为该患者及家系成员的临床诊断及遗传咨询提供了理论依据。ObjectiveTo explore the relationship between pathogenic gene,mutation and phenotype of left ventricular noncompaction(LVNC)patients and their family members.MethodsThe subjects were the proband with LVNC and her family members.The medical history including electrocardiogram,echocardiography and cardiac magnetic resonance examination of the proband and family members were collected.Whole exome sequencing of the proband was performed,bioinformatics analysis focused on the genes related to hereditary cardiomyopathy.Candidate pathogenic sites were validated by Sanger sequencing.The clinical interpretation of sequence variants were classified according to American College of Medical Genetics and Genomics(ACMG)guidelines.ResultsThe proband carried a heterozygous variation of the MYBPC3 gene c.C2827T and the MYH7 gene c.G2221C.The proband′s sister carried heterozygous variation of MYBPC3 gene c.C2827T.According to the ACMG guidelines,the variant was determined to be pathogenic.ConclusionThe missense variant of MYBPC3 gene c.C2827T and MYH7 gene c.G2221C are identified from the proband with LVNC and her family member,which provides a genetic basis for clinical diagnosis and genetic counseling of the patients and the family members with LVNC.

关 键 词：心肌病 左心室致密化不全 MYBPC3基因 MYH7基因 基因检测 

分 类 号：R541[医药卫生—心血管疾病]