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

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。

Objective:To explore the relationship between pathogenic gene, mutation and phenotype of left ventricular noncompaction (LVNC) patients and their family members.Methods:The 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.Results:The 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.Conclusion:The 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.