摘要
目的 研究中国人家族性肥厚型心肌病相关致病基因 ,揭示致病基因型与临床表型的关系。方法 在 6 0例门诊肥厚型心肌病患者及 6 0例正常对照中进行 β 肌球蛋白重链 (β MHC)基因突变扫描 ,聚合酶链反应扩增其功能区外显子基因片断 ,测序检测突变。对阳性结果者进行家系调查 ,限制性片断长度多态性分析其他家系成员。结果 在一患者及其家系中发现位于 β MHC基因第18号外显子的 6 6 3密码子位置发生C→T转换 ,使精氨酸变为半胱氨酸 ,该突变以前未见报道 ;在另两个患者及其家系中同样在 6 6 3密码子位置发生G→A转换 ,使精氨酸变为组氨酸。 3个家系基因型类似但临床表型不同。前者表现为进行性心力衰竭、心房颤动 ,外显率 10 0 % ;而后者临床表现则相对轻微 ,呈不完全外显。另外 5 7例患者和 6 0例正常对照未发现异常。结论 β MHC同一位置基因突变表现为不同的临床表型 ,提示即使是在同一种族 (中国人群 )中肥厚型心肌病亦存在异质性遗传特点。
Objective To study the disease causing gene mutations in Chinese familial hypertrophic cardiomyopathy and to reveal the relationship between the genotype and the phenotype Methods Sixty unrelated clinic patients with hypertrophic cardiomyopathy and 60 controls were chosen for the study Exons in the functional regions of beta myosin heavy chain(β MHC) gene were amplified with the polymerase chain reaction, DNA sequencing was used to detect the mutation Restriction fragment length polymorphism analysis was performed to screen the family members Results One patient and her pedigree had a C to T transversion in the codon 663,resulted in the arginine converted to cysteine The Arg663Cys mutation is also a previously unreported mutation in familial hypertrophic cardiomyopathy Two patients and their pedigrees had a G to A transversion in the β MHC gene codon 663,resulted in the arginine converted to histidine However, the three pedigrees with the same codon 663 mutation had different phenotype The first kind of mutation showed progressive heart failure, atrial fibrillation and 100% penetrance, while the phenotype of the second kind was clinically mild and lower penetrance The other 57 patients and the 60 controls were normal in the genetic test Conclusion The same codon mutation in the β MHC gene may have different clinical manifestations It implies that the genetic heterogeneity of the hypertrophic cardiomyopathy still exist even in the same race(such as Chinese population)
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2002年第3期131-135,共5页
Chinese Journal of Cardiology
