CAJ | 학술논문

目的识别一汉族家族性肥厚型心肌病(FHCM)家系的致病基因,分析其基因型与表型关系.方法收集到一个规模较大的FHCM家系,共5代89位成员,采集外周血标本,抽提基因组DNA.应用美国ABI PRISM 3700 DNA自动测序仪进行全基因组扫描,连锁分析确定初步致病基因的初步区域后,进一步进行精细定位和单倍型分析,搜索候选基因并明确致病基因.结果该家系共14例患者(4例已经去世,其中2例是年轻时猝死),在世的10例患者的左心室壁厚度均超过13 mm.该家系遗传方式符合常染色体显性遗传病的特点,通过全基因组扫描和连锁分析,在微卫星标记D1S249处获得最大概率对数值,为3.45(重组率θ=0.15).通过精细定位将致病基因所在位置确定为一号染色体长臂3区2带(1q32),该区域中含有肌钙蛋白T基因(TNNT2).结论该家系的致病基因位于染色体1q32,TNNT2基因位于该区域,是重要的候选基因.
목적 식별일한족가족성비후형심기병(FHCM)가계적치병기인,분석기기인형여표형관계.방법 수집도일개규모교대적FHCM가계,공5대89위성원,채집외주혈표본,추제기인조DNA.응용미국ABI PRISM 3700 DNA자동측서의진행전기인조소묘,련쇄분석학정초보치병기인적초보구역후,진일보진행정세정위화단배형분석,수색후선기인병명학치병기인.결과 해가계공14례환자(4례이경거세,기중2례시년경시졸사),재세적10례환자적좌심실벽후도균초과13 mm.해가계유전방식부합상염색체현성유전병적특점,통과전기인조소묘화련쇄분석,재미위성표기D1S249처획득최대개솔대수치,위3.45(중조솔θ=0.15).통과정세정위장치병기인소재위치학정위일호염색체장비3구2대(1q32),해구역중함유기개단백T기인(TNNT2).결론 해가계적치병기인위우염색체1q32,TNNT2기인위우해구역,시중요적후선기인.
Objective To identify the disease-causing gene and to investigate the genotype-phenotype correlation in a Chinese pedigree with familial hypertrophic cardiomyopathy (FHCM).Methods In this study,a fivegeneration family that consisted of 89 individuals with FHCM was identified.Total genome DNA was extracted from 67 subjects' peripheral leucocytes.A genome-wide screening was carried out using micro-satellite markers on ABI PRISM 3700 DNA sequencer.A linkage analysis was performed using the MLINK program.Results Fourteen family members had hypertrophic cardiomyopathy.Analysis by echocardiography showed all living affected individuals had a maximal left-ventricular-wall thickness of at least 13 mm.A two-point LOD score of 3.45 (θ =0.15),suggestive of linkage,was initially obtained with microsatellite marker D1S249.The FHCM causing gene,cardiac troponin T gene was located in this area.Conclusions The disease locus is mapped to chromosome 1 q32 in this family.As one of the aetiological genes for FHCM,it is reasonable to screen for mutations in the cardiac troponin T gene.