家族性肥厚型心肌病易感基因与HLA-DQ位点相关性分析

本文报道应用ＰＣＲ／ＳＳＯ方法分析了４个无肌凝蛋白重链基因突变的肥厚型心肌病多发家系成员ＨＬＡ－ＤＱ基因多态性，进行患病同胞共享ＨＬＡＤＱＡ１／ＤＱＢ１单倍型分析和Ｌｏｄｓ分析。结果表明，本病的易感基因与ＨＬＡ－ＤＱ基因存在连锁关系。提示在ＨＬＡ－ＤＱ座位附近可能存在与家族性肥厚型心肌病易感性有关的致病基因。     

原发性肥厚型心肌病与HLA0DQ的相关性研究

本文用ＰＣＲ／ＳＳＯ方法对４１例原发性肥厚型心肌病患者和５２例正常人ＨＬＡ－ＤＱＡ１和ＤＱＢ１基因的多态性进行分析。发现，在肥厚型心肌病患者中，ＤＱＡ１＊０２０１，ＤＱＢ１＊０５０４，０５０２等位基因频率明显较低，其相对风险值分别为９．５１、５．８７和１１．６０；而ＤＱＡ１＊０５０１，ＤＱＢ１＊０３０３１的频率明显地高，相对风险值分别为２．９３和６．６５。初步认为，原发性肥厚型心肌病与某些ＨＬＡ－     

山西汉族原发性干燥综合征与HLA-DQ基因多态性相关性的研究

目的:探讨山西汉族人群原发性干燥综合征(pSS)与HLA-DQ等位基因的相关性,从基因水平上探索pSS的发病机制。方法:应用聚合酶链反应-序列特异性引物(PCR-SSP)法对pSS患者与健康对照进行HLA-DQA1、HLA-DQB1基因的分型;采用χ2检验和Fisher’s精确检验比较两组各等位基因频率的差异。结果:(1)在100例山西汉族健康人及pSS患者中,HLA-DQA1*0501基因频率分别为12.0%和22.0%。与健康对照相比较,pSS患者中HLA-DQA1*0501基因频率显著增高(χ2=7.087,P<0.05,RR=2.068)。(2)pSS患者HLA-DQA1*0301/2等位基因频率为13.0%,显著低于健康对照组的24.5%(χ2=8.681,P<0.05,RR=0.460)。(3)pSS患者中HLA-DQB1*0201基因频率为28.5%,显著高于健康人的18.5%(χ2=5.563,P<0.05,RR=1.756)。结论:HLA-DQA1*0501和HLA-DQB1*0201等位基因可能是山西汉族pSS的易感基因,而HLA-DQA1*0301/2等位基因可能是其保护基因。     

新生儿先天性肥厚型心肌病1例

病例 :患儿 ,男 ,7天 ,Ｇ3Ｐ3,足月分娩 ,出生体重 34 0 0ｇ ,生后全身青紫 ,未经处理约 1小时后 ,青紫略好转。 1天前 ,患儿无明显诱因出现拒奶 ,恶心 ,不哭、少动于 1999 8 2 7入院。其二姐因“脑积水”于 8个月时死亡 ,否认有家族性遗传病及传染病史。查体 :Ｔ37℃Ｐ130次 /分 ,Ｒ40次 /分 ,发育正常 ,营养中等 ,神志清 ,呼吸急促 ,反应差。全身皮肤粘膜黄染 ,头颅大小、形态正常 ,四肢末端紫绀 ,双肺呼吸音粗糙 ,未闻及干湿性罗音 ,心率 130次 /分 ,律齐 ,心音有力 ,心前区可闻及 4/ 6级粗糙的收缩期吹风样杂音 ,传导广泛 ,伴震颤。肝肋…     

肥厚型心肌病分子遗传学研究进展

肥厚型心肌病(hypertrophic cardiomyopathy,HCM)是一种以常染色体显性遗传为特征的具有遗传异质性的心脏疾病,它是年轻人心源性猝死的首要病因。已发现至少有18种基因的突变可导致家族性肥厚型心肌病,加深对其分子遗传学的认识有利于促进该病的诊断和治疗。现就家族性肥厚型心肌病近期分子遗传学的研究进行了总结。     

线粒体DNA点突变与肥厚型心肌病的关系

肥厚型心肌病 (hypertrophic cardiomyopathy,HCM)是以心肌肥厚、心肌纤维排列紊乱为特征的一种特发性心肌病。已证实 HCM是儿童及青年人猝死最常见原因之一 ,发生率为1%～ 6 % [1 ,2 ]。由于该病临床表现多样 ,部分患者可在无任何症状且心电图、超声心动图未出现异常的情况下因剧烈运动发生猝死 ,因此 ,从分子水平对 HCM进行研究 ,对于阐明该病的发生机理 ,早期诊断、防治具有重要意义。有些学者 [3- 6 ] 研究发现某些 HCM与线粒体 (mt DNA)的缺失和点突变有关。我们应用PCR、PCR- SSCP及 PCR产物直接银染测序技术 ,对 19例HC…     

家族性肥厚型心肌病与肌钙蛋白T

家族性肥厚型心肌病(FHCM)是一种常染色体显性遗传病, 由于编码心肌蛋白的基因突变引起,目前已识别出至少13个不同致病基因的200余种突变。目前,阐明FHCM的分子遗传学机制已经成为当前研究的热点之一。肌钙蛋白T通过与原肌宁蛋白结合,在将肌钙蛋白复合体锚钉到细肌丝上起重要作用。肌钙蛋白T基因突变是导致家族性肥厚型心肌病的主要原因,至今已经发现了大约30个突变,约占所有突变的15~20%。肌钙蛋白T基因突变所致FHCM有两个主要特征：（1）心肌肥厚程度较轻, 疾病外显率差别较大,（2）猝死率高。目前所发现的致FHCM突变,主要集中在肌钙蛋白T的T1和T2结构域。对肌钙蛋白T突变致FHCM分子机制的研究将有助于肥厚型心肌病的基因诊断和临床治疗。     

心尖肥厚型心肌病患者心电图表现与临床诊断意义

目的：探讨心尖肥厚型心肌病患者的心电图特征性改变及临床诊断意义.方法：分析68例心尖肥厚型心肌病患者的心电图及超声心动图资料.结果：心尖肥厚心肌病合并有心电图异常和超声心动图异常改变者68例,中胸及左胸导联,巨大倒置酷似“冠状T波”≥0.2～0.3mV,以V3,V4明显且TV4＞TV5＞TV3者62例;左胸V4-V6导联R波电压增高,且RV4＞RV5＞RV6者60例;ST段压低以V3-V4最明显者62例;超声心动图示心尖肥厚达17mm或以上伴心尖部心腔狭小者68例.结论：心电图对心尖肥厚型心肌病具有早期诊断价值 。     

成年人肥厚型心肌病表型的临床诊治研究进展

很多遗传代谢性心肌病可表现为肥厚型心肌病表型,但导致心肌肥厚的病因各不同,其治疗策略、预后也不相同。由于部分遗传代谢性心肌病在明确病因后进行病因治疗可以明显改善心功能状态,甚至完全逆转心肌病变。早期诊断、识别和治疗以左心室肥厚为主要表型的遗传代谢性心肌病尤为重要。笔者综述肥厚型心肌病、心脏淀粉样变、AndersonFabry病、线粒体心肌病及Danon病等表现为肥厚型心肌病表型的遗传性代谢性心肌病,分析其发病机制、临床表现,超声心动图特点,总结诊断及治疗方法。对于遗传代谢性心肌肥厚患者的超声心动图,大多无特异性,早期诊断还存在一定难度。因此,在日常工作中需要提高警惕,详细询问病史,结合相关生物化学检查和组织病理改变,甚至基因检查进行明确诊断。     

Thromboembolism in Patients with Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease, which has a marked heterogeneity in clinical expression, natural history, and prognosis. HCM is associated with a high prevalence of thromboembolic events (stroke and systemic embolic events), even if taking no account of atrial fibrillation (AF), leading to unexpected disability and death in patients of all ages. Several risk factors of thromboembolism such as AF, greater age, left atrial diameter, heart failure and others have been confirmed in patients with HCM. Conventional thromboembolic predictive models were estimated by several trials in HCM population but it turned out to be unsatisfactory. Based on those previous explorations, researchers tried to modify or develop novel models suitable for HCM population in thromboembolism prediction. In consideration of catastrophic advent events of thromboembolism, current guidelines have recommended life-long anticoagulant therapy after a single short AF.Therefore, early identification of risk factors for thromboembolism, accurate risk stratification, timely preventive measures and aggressive management may help to avoid serious adverse thromboembolic events in HCM population.     

中国人群肥厚型心肌病MYH7基因突变的研究与展望

肥厚型心肌病( hypertrophic cardiomyopathy, HCM)是一种以左心室或室间隔不对称性肥厚为基本特征的最常见遗传性心脏病,该病是青少年及年轻运动员猝死的最主要原因。先天基因缺陷是HCM主要的分子遗传学基础,其遗传方式遵循常染色体显性遗传模式。与HCM发病相关的基因较多,其中编码心脏β-肌球蛋白重链(cardiac beta-myosin heavy chain, MYH7)基因为HCM最主要的致病基因。通过查阅文献,检索到目前已报道的587例中国HCM患者被进行MYH7基因突变筛查,统计结果表明：共有150例中国HCM患者由MYH7基因外显子上的66个致病性突变所致。对已报道的中国HCM人群MYH7基因的突变特点进行总结和分析,这将为中国HCM人群的诊断、预防和治疗提供参考依据。     

Pathomorphological Variants of Midventricular Obstruction of Interventricular Septum during Hypertrophic Cardiomyopathy

Postmortem contrast cardiac ventriculography, coronarography, volume-mass and planimetric cardiometry, as well as echocardiography and pathomorphological data correlation technique were employed for examination of the hearts from patients died from hypertrophy cardiomyopathy (n=100). The following variants of midventricular hypertrophy of the interventricular septum (midventricular obstruction) were established: midleft ventricular, midright ventricular, midproximal, midmaximal. Isolated distal apex hypertrophy and apical hypertrophy were also documented. These variants and forms of cardiac pathology are determined by peculiar changes in geometrical structure of the septum and left ventricle. Multiplanar variability and mobility of interventricular septum combined with peculiar catenary shape promote specific abnormalities of intracardiac hemodynamics determining dissociation between the echocardiographic and pathomorphological diagnostic data and underlying the leading elements of patho- and thanatogenesis of hypertrophic cardiomyopathy.     

肥厚型心肌病分子研究进展

肥厚型心肌病(hypertrophic cardiomyopathy,HCM)是常见遗传性心血管疾病,其发病率可达1/500.该病是目前年轻运动员心源性猝死的重要病因,可在各个年龄段发病,其中50％～70％HCM由基因突变所致.近年来,HCM的分子研究已取得较大进展,本文就HCM相关的主要致病基因及其分子机制作一综述.     

MTO1 Mutations are Associated with Hypertrophic Cardiomyopathy and Lactic Acidosis and Cause Respiratory Chain Deficiency in Humans and Yeast

We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial‐tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype.     

QRS-T angle in patients with Hypertrophic Cardiomyopathy - A comparison with Cardiac Magnetic Resonance Imaging

Objective: We sought to investigate the possible association of a wide QRS-T angle on the surface EKG and myocardial fibrosis on contrast-enhanced cardiovascular magnetic (CMR) imaging in patients with hypertrophic cardiomyopathy (HCM).Background: Risk stratification in HCM patients is challenging. Late gadolinium enhancement (LGE) visualizes myocardial fibrosis with unique spatial resolution and is a strong and independent prognosticator in these patients. The QRS-T angle from the surface EKG is a promising prognostic marker in various cardiac pathologies.Methods: 70 patients with HCM obtained a standardized digital 12-lead EKG for the calculation of the QRS-T angle and underwent comprehensive CMR imaging for visualization of fibrosis by LGE. Patients were divided into groups according to the absence or presence of fibrosis on CMR.Results: 43 of 70 patients with HCM showed LGE on CMR following contrast administration. HCM patients with LGE (fibrosis) had wider QRS-T angles as compared to the patient group without LGE (100±54 vs. 46±31; <0.001). A QRS-T angle of 90 degrees or more was a strong predictor (OR 32.84, CI 4.08-264.47; p <0.001) of HCM with LGE.Conclusion: There is a strong association of a wide QRS-T angle and myocardial fibrosis in patients with HCM.     

扩张型心肌病与缺血性心肌病二维彩色多普勒的对比研究

利用二维彩色多普勒在心脏形态学、血液动力学及心室功能方面对扩张型心肌病 (DCM )及缺血性心肌病 (ICM )进行诊断及鉴别诊断。利用二维彩色多普勒技术分别测定 5 2例DCM组、ICM组及正常对照组的数据 ,利用定量和半定量的方法对数据进行测定 ,用统计学对数据进行处理。结果表明正常组分别与DCM组及ICM组比较有显著的差异 (P <0 0 5或0 0 1) ,ICM组与DCM组有比较显著的差异 (P <0 0 1)。DCM组主要是心肌弥漫性改变 ,心腔普遍扩大 ,心脏收缩功能明显减退 ,舒张功能为“正常”。多瓣膜返流发生率高且严重。ICM组以心肌局部病变为主 ,主要是左心腔扩大 ,左室收缩功能正常或轻度减低 ,舒张功能明显减低。瓣膜多为单瓣膜返流且较轻。结论 :二维彩色多普勒是临床鉴别诊断DCM和ICM最可靠、最简单及无创伤的首选方法。     

血管紧张素原基因M235T多态性与肥厚型心肌病的关系

目的　探讨血管紧张素原 ( angiotensinogen,AGT)基因 M2 35 T变异与肥厚型心肌病( hypertrophic cardiomyopathy,HCM)的关系。方法　对 72例 HCM患者与 80名正常对照者进行病例 -对照研究。采用聚合酶链反应与限制性片段长度多态性技术检测 AGT基因 M2 35 T变异。同时通过 M型二维超声心动图分别测量室间隔、左室后壁和心尖部心肌厚度。结果　 ( 1)经 PCR扩增及 Tth111 酶切 ,AGT基因型有 3种形式 :MM、TT与 MT基因型。两组 AGT基因型的分布均符合 Hardy- Weinberg平衡。 ( 2 )AGT基因 M2 35 T基因型在 HCM组与对照组的分布差异有显著性 ( χ2 =6 .0 90 ,P<0 .0 5 )。HCM组 TT基因型与 T2 35等位基因的频率均高于对照组 ( TT基因型 :0 .6 3vs0 .4 5 ,OR=2 .0 37,95 % CI:1.0 6 4～7.899,P<0 .0 5 ;T2 35等位基因 :0 .78vs0 .6 4 ,OR=1.990 ,95 % CI:1.197～ 3.30 8,P<0 .0 1)。 ( 3) HCM组TT基因型患者左室壁最厚处平均厚度明显大于 MM、MT基因型患者 [( 19.1± 4 .8) mm vs( 15 .3± 2 .6 )mm与 ( 16 .2± 5 .1) mm,F=4 .2 6 1,P<0 .0 5 ]。结论　 AGT基因 M2 35 T变异与 HCM的发病显著相关 ,TT基因型或 T2 35等位基因可能是参与 HCM发生及加重心肌肥厚的一个遗传方面的危险因素     

基于靶基因文库的高通量测序平台建立肥厚型心肌病患者致病基因突变检测方法

目的 基于靶基因文库,应用下一代半导体高通量测序平台,建立快速、 准确的肥厚型心肌病(hypertrophic cardiomyopathy,HCM)常见致病基因突变检测方法 ,有利于HCM患者的早期预防及临床分子诊断.方法 选择国内外公认的与HCM致病相关的常见基因(MYH7、MYBPC3、TNNT2、TNNI3、A...