BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress ...BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress to a dilated phase of HCM(DPHCM),which is associated with a poor prognosis;however,the underlying pathogenesis remains inadequately understood.CASE SUMMARY In this study,we present a case involving a pedigree with familial DPHCM and conduct a retrospective review of patients with DPHCM with identified gene mutations.Through panel sequencing targeting the coding regions of 312 genes associated with inherited cardiomyopathy,a heterozygous missense mutation(c.746G>A,p.Arg249Glu)in the MYH7 gene was identified in the proband(III-5).Sanger sequencing subsequently confirmed this pathogenic mutation in three additional family members(II-4,III-4,and IV-3).A total of 26 well-documented patients with DPHCM were identified in the literature.Patients with DPHCM are commonly middle-aged and male.The mean age of patients with DPHCM was 53.43±12.79 years.Heart failure,dyspnoea,and atrial fibrillation were the most prevalent symptoms observed,accompanied by an average left ventricular end-diastolic size of 58.62 mm.CONCLUSION Our findings corroborate the pathogenicity of the MYH7(c.746G>A,p.Arg249Glu)mutation for DPHCM and suggest that the Arg249Gln mutation may be responsible for high mortality.展开更多
目的在致病突变明确的家系中通过产前遗传诊断来阻断肥厚型心肌病(hypertrophy cardiomyopathy,HCM)的代际传递,减少HCM患者数量。方法对分别携带MYH7基因Arg663Ser和Arg453His致病突变的2例HCM患者进行家系分析,通过Sanger测序检测致...目的在致病突变明确的家系中通过产前遗传诊断来阻断肥厚型心肌病(hypertrophy cardiomyopathy,HCM)的代际传递,减少HCM患者数量。方法对分别携带MYH7基因Arg663Ser和Arg453His致病突变的2例HCM患者进行家系分析,通过Sanger测序检测致病突变位点,通过毛细管电泳进行短串联重复序列(short tandem repeats,STR)分型及及连锁分析。在17-20周行羊穿术采集羊水,羊水细胞提取基因组DNA,进行遗传检测。结果MYH7基因Arg663Ser和Arg453His突变在各自家系中与HCM家系共分离,为所在家系的致病突变。我们选择了杂合度高的6个位于MYH7基因附近的STR(D14S50、D14S283、D14S990、D14S972、D14S64和D14S264)进行分型检测,确认在第一个家系中D14S50的173bp长度等位基因和D14S990的151bp长度等位基因与Arg663Ser突变连锁。在第二个家系中,D14S50的169bp长度等位基因和D14S283的145bp长度等位基因与Arg453His突变连锁。羊水DNA的Sanger测序和STR分型均显示2例胚胎均未携带MYH7基因致病突变。新生儿脐带血的复检结果与产前诊断结果一致。结论产前遗传诊断能够在孕早期明确诊断胎儿是否携带家族HCM致病突变,为咨询者夫妇提供合理的遗传咨询依据,对阻断HCM在家系中遗传具有重要意义。展开更多
肥厚型心肌病(hypertrophic cardiomyopathy,HCM)是儿童中最常见的单基因遗传性心肌病。肌节基因[β-肌球蛋白重链(cardiac beta-myosin heavy chain,MYH7)、MYBPC3等基因]突变是HCM最常见的遗传学病因,其中以MYH7基因突变最常见,占30%~...肥厚型心肌病(hypertrophic cardiomyopathy,HCM)是儿童中最常见的单基因遗传性心肌病。肌节基因[β-肌球蛋白重链(cardiac beta-myosin heavy chain,MYH7)、MYBPC3等基因]突变是HCM最常见的遗传学病因,其中以MYH7基因突变最常见,占30%~50%。MYH7基因突变具有受环境因素影响、可合并多个基因变异,以及年龄依赖的外显率等特点,使患儿临床表型不一或重叠,包括多种心肌病和骨骼肌疾病。目前关于MYH7基因突变导致儿童HCM的发病机制、病程及预后尚不明确。该文通过总结MYH7基因突变导致HCM可能的发病机制、临床表型及治疗,以期有利于患儿的精准预后评估、个体化管理及治疗。展开更多
基金Supported by National Natural Science Foundation of China,No.81770379.
文摘BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress to a dilated phase of HCM(DPHCM),which is associated with a poor prognosis;however,the underlying pathogenesis remains inadequately understood.CASE SUMMARY In this study,we present a case involving a pedigree with familial DPHCM and conduct a retrospective review of patients with DPHCM with identified gene mutations.Through panel sequencing targeting the coding regions of 312 genes associated with inherited cardiomyopathy,a heterozygous missense mutation(c.746G>A,p.Arg249Glu)in the MYH7 gene was identified in the proband(III-5).Sanger sequencing subsequently confirmed this pathogenic mutation in three additional family members(II-4,III-4,and IV-3).A total of 26 well-documented patients with DPHCM were identified in the literature.Patients with DPHCM are commonly middle-aged and male.The mean age of patients with DPHCM was 53.43±12.79 years.Heart failure,dyspnoea,and atrial fibrillation were the most prevalent symptoms observed,accompanied by an average left ventricular end-diastolic size of 58.62 mm.CONCLUSION Our findings corroborate the pathogenicity of the MYH7(c.746G>A,p.Arg249Glu)mutation for DPHCM and suggest that the Arg249Gln mutation may be responsible for high mortality.
文摘目的在致病突变明确的家系中通过产前遗传诊断来阻断肥厚型心肌病(hypertrophy cardiomyopathy,HCM)的代际传递,减少HCM患者数量。方法对分别携带MYH7基因Arg663Ser和Arg453His致病突变的2例HCM患者进行家系分析,通过Sanger测序检测致病突变位点,通过毛细管电泳进行短串联重复序列(short tandem repeats,STR)分型及及连锁分析。在17-20周行羊穿术采集羊水,羊水细胞提取基因组DNA,进行遗传检测。结果MYH7基因Arg663Ser和Arg453His突变在各自家系中与HCM家系共分离,为所在家系的致病突变。我们选择了杂合度高的6个位于MYH7基因附近的STR(D14S50、D14S283、D14S990、D14S972、D14S64和D14S264)进行分型检测,确认在第一个家系中D14S50的173bp长度等位基因和D14S990的151bp长度等位基因与Arg663Ser突变连锁。在第二个家系中,D14S50的169bp长度等位基因和D14S283的145bp长度等位基因与Arg453His突变连锁。羊水DNA的Sanger测序和STR分型均显示2例胚胎均未携带MYH7基因致病突变。新生儿脐带血的复检结果与产前诊断结果一致。结论产前遗传诊断能够在孕早期明确诊断胎儿是否携带家族HCM致病突变,为咨询者夫妇提供合理的遗传咨询依据,对阻断HCM在家系中遗传具有重要意义。
文摘肥厚型心肌病(hypertrophic cardiomyopathy,HCM)是儿童中最常见的单基因遗传性心肌病。肌节基因[β-肌球蛋白重链(cardiac beta-myosin heavy chain,MYH7)、MYBPC3等基因]突变是HCM最常见的遗传学病因,其中以MYH7基因突变最常见,占30%~50%。MYH7基因突变具有受环境因素影响、可合并多个基因变异,以及年龄依赖的外显率等特点,使患儿临床表型不一或重叠,包括多种心肌病和骨骼肌疾病。目前关于MYH7基因突变导致儿童HCM的发病机制、病程及预后尚不明确。该文通过总结MYH7基因突变导致HCM可能的发病机制、临床表型及治疗,以期有利于患儿的精准预后评估、个体化管理及治疗。
