CAJ | 학술논문

目的:研究中国汉族人群家族性肥厚型心肌病(FHCM)患者的致病基因突变位点,分析其基因型与表型关系.方法:对6个家系先证者行肌球连接蛋白-C基因(MYBPC3)筛查,聚合酶链反应扩增其MYBPC3基因13、15-16、26、及 27号功能区外显子片断,双脱氧末端终止法测序.对阳性结果者家系中其他成员及健康对照组同一位置筛查,分析患者基因型及临床表型特点.结果:在2个家系中,同时发现MYBPC3基因Val896Met杂合突变,而健康对照组同一位置未见异常,2家系中共6人携带此突变,其中发病5例;该突变可能为我国汉人FHCM家系中首次发现.结论: MYBPC3是我国汉族FHCM患者的常见致病基因;MYBPC3基因Val896Met突变所致肥厚型心肌病外显率高、临床症状出现较晚、进展缓慢、出现明显年龄依赖性特点,为一种良性突变.
목적:연구중국한족인군가족성비후형심기병(FHCM)환자적치병기인돌변위점,분석기기인형여표형관계.방법:대6개가계선증자행기구련접단백-C기인(MYBPC3)사사,취합매련반응확증기MYBPC3기인13、15-16、26、급 27호공능구외현자편단,쌍탈양말단종지법측서.대양성결과자가계중기타성원급건강대조조동일위치사사,분석환자기인형급림상표형특점.결과:재2개가계중,동시발현MYBPC3기인Val896Met잡합돌변,이건강대조조동일위치미견이상,2가계중공6인휴대차돌변,기중발병5례;해돌변가능위아국한인FHCM가계중수차발현.결론: MYBPC3시아국한족FHCM환자적상견치병기인;MYBPC3기인Val896Met돌변소치비후형심기병외현솔고、림상증상출현교만、진전완만、출현명현년령의뢰성특점,위일충량성돌변.
Objective:Familial hypertrophic cardiomyopathy (FHCM) is a form of cardiomyopathy with an autosomal dominant inherited disease, which is caused by mutations in at least one of the sarcomeric protein genes. Mutations in the myosin binding protein C genes (MYBPC3) are the more common cause of HCM. This study was to reveal the disease-causing gene mutations in Chinese population with FHCM, and to analyze the correlation between the genotype and phenotype. Method:We sequenced exons 13,15-16,26 and 27 of the MYBPC3 gene in 6 families with hypertrophic cardiomyopathy (HCM) from the region of Anhui province in China; Genomic DNA was amplified, and fragments were directly sequenced. Each DNA variant found in the patients was also analyzed in 80 healthy controls through automatic sequencing. Result:The mutation of V896M in two Chinese families with HCM was detected for the first time in China. With a G→G/A transversion in nucleotide 16750 of the MYBPC3 gene, the replacement of valine by methionine, took place at amino acid residue 896. A two-dimensional echocardiogram showed moderate asymmetrical septal hypertrophy. There was no obstruction in the left ventricular outflow tract in all patients. In two families, a total of 5 individuals were diagnosed HCM and 1 of them were healthy man. The DNA variant was not detected in 80 healthy controls.Conclusion:The mutation of V896M in MYBPC3 is a benign type. Moreover, the heart function of the people evidently more deteriorative when their age are more older. The mutation has been reported in the first in China.