摘要
目的研究中国人肥厚型心肌病致病基因,分析基因型与临床表型的关系。方法在一肥厚型心肌病家系中进行心脏型肌球蛋白结合蛋白 C 基因(MYBPC3)和β-肌球蛋白重链基因(MYH7)突变筛查,利用聚合酶链反应(PCR)扩增其功能区的外显子片段,双脱氧末段终止法测序。家系调查资料包括临床表现、体格检查、心脏超声和心电图。结果在该家系27例有血缘关系的研究对象中9例携带 MYBPC3 13261 G>A(G758D)突变,正常对照组同一位置未见异常。该突变位点是 MYBPC3基因第23号外显子的甘氨酸突变为天冬氨酸,其中2例携带者发病,一例表现为心室扩大,左室射血分数减低等扩张型心肌病样表现,伴室间隔不对称肥厚,厚度为14 mm,另外一例患者为典型的肥厚型心肌病表现。MYH7基因未发现突变。结论 MYBPC3基因13261 G>A 突变是该肥厚型心肌病家系的致病突变,其外显率为22%,其中一例患者表现为肥厚型心肌病的扩张相,MYBPC3基因 G758D 突变可能是肥厚型心肌病进展为扩张型心肌病样改变的原因之一。对临床表现为扩张型心肌病的患者进行家族史调查及基因检查十分必要。
Objective To study the disease-causing gene mutation in Chinese patients with hypertrophic cardiomyopathy （HCM） and to analyze the genotype and phenotype correlation. Methods One family （n = 27 ） affected with HCM were chosen for the study. The full encoding exons and flanking sequences of β-myosin heavy chain gene （MYH7） and cardiac myosin-binding protein C gene （MYBPC3） were amplified with PCR and the products were sequenced. The clinical data including symptom, physical, echocardiography and electrocardiography examinations were collected. Results We identified a 13261 G 〉 A mutation, which causes a misseuse mutation （G758D） in exon 23 of MYBPC3 in 9 family members. One mutation carrier suffered from dilated cardiomyopathy （DCM） with asymmetric interventricular septal hypertrophy （ 14 mm）. Another mutation carrier was diagnosed as HCM. Conclusions The 13261 G 〉 A mutation is associated with a DCM-like HCM and HCM phenotype in this Chinese family affected with HCM.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2007年第1期17-20,共4页
Chinese Journal of Cardiology
基金
北京市自然科学基金委员会资助2004年重大项目(704001)
关键词
心肌病
肥厚性
突变
表型
Cardiomyopathy,hypertrophic
Mutation
Phenotype
