肥厚型心肌病患者线粒体DNA点突变的研究

1990年ＯｚａｗａＴ等人首先报道肥厚型心肌病(ＨＣＭ)患者心肌细胞中存在线粒体ＤＮＡ(ｍｔＤＮＡ)的多重缺失。随后,ＺｅｖｉａｎｉＭ和ＳｉｌｖｅｓｔｒｉＧ等人在家族性及散发的心肌病患者中又分别发现ｍｔＤＮＡ3260、9997等位点的突变,这些点突变改变了进化上高度保守的氨基酸,被认为是某些ＨＣＭ的致病原因。在过去的研究中,我们也已发现在某些ＨＣＭ患者的ｍｔＤＮＡ中有缺失突变。最近我们应用聚合酶链反应ＤＮＡ单链构象多态技术(ＰＣＲＳＳＣＰ)及ＰＣＲ产物直接银染测序技术对26例散发的ＨＣＭ患者心肌、骨骼肌及血细胞共32份标…     

线粒体DNA点突变与心肌病关系的研究

用聚合酶链反应（ＰＣＲ）和异源双链（ＨＥＴ）凝胶电泳检测了１５例原发性扩张型心肌病（ＤＣＭ）、１３例急性心肌炎患儿及１个肥厚型心肌病（ＨＣＭ）家系中１７例成员 的外周血线粒体ＤＮＡ（ｍｔＤＮＡ）点突变。结果显示，ＤＣＭ患儿中，６例在ｍｔＤＮＡ保守区３１０８￣３７１７位存在点突变，其中１例家族性ＤＣＭ患儿及其母亲均检出点突变，提示ｍｔＤＮＡ点突变在ＤＣＭ发病中起一定作用；１３例急性心肌炎患儿中有１例     

线粒体DNA与心肌病的关系

人类线粒体DNA（mtDNA）是细胞内唯一存在于细胞核外的遗传物质,参与了转录、编码2个rRNA,22个tRNA及线粒体呼吸链中的13种蛋白多肽亚单位。人类某些疾病与线粒体DNA缺陷有关。心肌病是一类原因不明的伴随心脏功能障碍的心肌疾病。研究显示,线粒体产生的大量活性氧可导致mtDNA缺失或突变,tRNA基因保守序列突变影响肌肉收缩蛋白合成,造成氧化磷酸化缺陷,影响能量代谢。因此,线粒体的功能缺陷可能在心肌病的发生发展中起一定的作用。本文探讨了mtDNA突变与心肌病的关系,对mtDNA的深入研究将为临床寻找病因以及预防、诊断、治疗心肌病提供新思路。     

扩张型心肌病患儿线粒体DNA缺失的研究

采用PCR法检测了15例扩张型心肌病（DCM）、13例急性心肌炎（病程＜3个月）患儿和10例正常儿童外周血淋巴细胞中线粒体DNA（mtDNA）的缺失情况,以研究mtDNA突变在DCM发病中的作用。结果显示,被检者线粒体均存在5Kb和7.4Kb的mtDNA缺失,但DCM患儿的缺失率显著高于心肌炎患儿和正常儿童（缺失率分别为7.97±3．51％,2.5±1．64％和2.28±1．76％,P＜0．05）。提示mtDNA缺失与部分DCM的发病有关。     

肥厚型心肌病研究进展

肥厚型心肌病研究进展上海市第二军医大学长征医院陈振云综述张国元审校肥厚型心肌病（ＨＣＭ）是遗传性心肌病之一，临床上虽相对少见但由于其临床表现及病理生理变化多变，治疗困难顶后差，约５０％病人发生猝死（ＳＤ）［１，２］。故临床医师应加强对本病的认识，提高...     

病毒性心肌炎与扩张型心肌病心肌线粒体DNA缺失的定量分析

目的对比研究病毒性心肌炎(VMC)与扩张型心肌病(DCM)患者活检心肌组织线粒体DNA(mtDNA)缺失突变情况及其与外周淋巴细胞mtDNA缺失程度的相关性.方法用定量PCR法检测20例VMC患者、12例DCM患者心肌细胞及其外周血淋巴细胞mtDNA4977碱基对(mtDNA4977)和mtDNA7436碱基对(mtDNA)缺失率.取12例健康意外死亡者心肌和23例献血员外周血淋巴细胞作正常对照.结果正常对照者、VMC和DCM患者心肌细胞均存在mtDNA4977及mtDNA7436缺失,合计缺失率分别为0.175%、0.385%和3.004%;外周淋巴细胞mtDNA缺失程度与心肌细胞呈一致性改变,且有良好的相关性(r=0.960,P＜0.001).结论mtDNA缺失可能是VMC发病及其向DCM演变的一个重要心肌损伤机制;外周淋巴细胞在研究心肌细胞mtDNA缺失中的作用值得进一步探讨.     

肥厚型心肌病心律失常与心肌离子通道突变的关系

目的:探讨肥厚型心肌病(HCM)患者是否存在与心律失常有关的通道改变。方法:以PCR加SSCP方法对24例HCM患者心肌离子通道IKr、IKs和INa的编码基因KvLQT1、HERG、SCN5A进行筛查。正常对照100例。结果:在其中伴严重室性心律失常(短阵室性心动过速及因室性心动过速频发而安装ICD)的12例HCM患者中发现2例存在KvLQT1基因突变,分别为Pro448Arg突变和Val607Ala/Ile608Leu/Met619Leu三突变串联,后一种突变为首次报道。在其余无明显心律失常的12例HCM患者和正常对照中未发现突变。结论:心肌离子通道突变可能是部分HCM患者发生严重心律失常的机制之一。     

肥厚型心肌病患者的心电图改变

肥厚型心肌病的病理改变主要以心室肌肥厚为特征,并且还会影响到左心室以及室间隔,很多是非对称性左室肥厚。该病的心电图异常率和患者有无症状、室间隔肥厚程度密切相关。而ST-T异常是肥厚型心肌病较常见的心电图表现之一。本文主要对肥厚型心肌病,尤其是心尖肥厚型心肌病的心电图改变现象进行综述。     

线粒体DNA突变与衰老

衰老又称老化,通常是指在正常状况下生物发育成熟后,随年龄增加,自身功能减退,内环境稳定能力与应激能力下降,结构、组分逐步退行性改变,趋向死亡,不可逆转的现象[1].1956年,Harman首先提出来衰老的自由基假说,之后又提出人类衰老过程中线粒体DNA是自由基攻击的首要目标.19世纪80年代初Miquel等提出"细胞衰老学说",认为衰老是由于氧自由基攻击线粒体DNA引起的一个生物过程.1989年Linnane等提出线粒体衰老假说.随着时代的发展与科技的进步,人们越来越关注线粒体与衰老的关系,线粒体与衰老的关系也成为研究前沿.\     

Apical Hypertrophic Cardiomyopathy in an Adolescent

To our knowledge, this is one of the few reported cases of apical hypertrophic cardiomyopathy in an adolescent patient in the United States. We describe a clinical presentation of an adolescent male who presented for cardiac evaluation and was found to have an apical variant of hypertrophic cardiomyopathy.     

中国肥厚型心肌病患者心脏型肌球蛋白结合蛋白C基因突变特点分析

目的观察中国肥厚型心肌病(HCM)患者心脏型肌球蛋白结合蛋白C基因(MYBPC3)突变的特点。方法在100例中国HCM患者中对MYBPC3基因的所有外显子及其侧翼内含子序列进行基因扫描,聚合酶链反应(PCR)扩增目的片段,双脱氧末段终止法测序。分析国人HCM患者基因突变的特点。结果 100例HCM患者中,10例患者携带9种MYBPC3基因突变,5种为错义突变,1种为剪接位点突变,1种为插入突变,2种为缺失突变。结论 MYBPC3基因是中国HCM人群的常见致病基因,并且MYBPC3基因突变形式多种多样,这是其主要的突变特点之一。     

心脏型肌球蛋白结合蛋白CG416S突变导致肥厚型心肌病

目的观察肥厚型心肌病(HCM)患者心脏型肌球蛋白结合蛋白CG416S突变导致肥厚型心肌病的特点。方法在100例HCM患者中对心脏型肌球蛋白结合蛋白C基因(MYBPC3)的所有外显子及其侧翼内含子序列进行基因扫描,聚合酶链反应(PCR)扩增目的片段,双脱氧末段终止法测序。分析携带基因突变患者的表型特点。结果在一例患者中发现MYBPC3第8697G>A基因突变,该突变位于外显子15,造成了心脏型肌球蛋白结合蛋白C第416位的甘氨酸转变成丝氨酸(G416S),该位置位于保守区。患者65岁时出现活动后胸痛不适,无高危因素。结论心脏型肌球蛋白结合蛋白CG416S错义突变能够导致HCM,携带该突变的患者表型轻、预后好。     

Hypertrophic Cardiomyopathy in a Neonate Associated with Nemaline Myopathy

Nemaline myopathy is a congenital nonprogressive skeletal muscle disorder with a characteristic rod body formation in the skeletal muscle fibers. Cardiac involvement in nemaline myopathy is rare, although both dilated and hypertrophic cardiomyopathy have been reported. We describe an infant diagnosed with hypertrophic cardiomyopathy and hypotonia on the first day of life. Muscle biopsy confirmed nemaline myopathy at 3 weeks of age. The diagnosis of nemaline myopathy precluded consideration of heart transplantation, thus shifting the focus to comfort care. This is the earliest presentation of hypertrophic cardiomyopathy reported in the literature in the setting of nemaline myopathy. The approach to determining an etiology for hypertrophic cardiomyopathy in an infant is reviewed.     

Clinical Analysis of 42 Patients With Hypertrophic Cardiomyopathy

Objectives To investigate the clinical manifestations of hypertrophic cardiomyopathy (HCM), and to find out the clinical clues to avoid misdiagnosis and provide reference for future clinical diagnosis and treatment. Methods A retrospective analysis of 42 consecutive patients with HCM hospitalized in our hospital between January 1995 and December 2002 was explored. Based on the family history of HCM, clinical manifestations, electrocar-diogram, echocardiogram, coronary angiography and left ventriculography, the clinical characteristics between HCM patients with left ventricular outflow tract obstruction (HOCM) and HCM patients without obstruction (HNOCM) were compared. The causes of misdiagnosis and losing diagnosis were analysis. Results 13 patients were in HOCM group and 29 patients were in HNOCM group. More patients with syncope were in HOCM group than in HNOCM group (6/13 vs. 2/29, P < 0.05). Patients with ejective murmur were in HOCM group only (P < 0.01). Left ventricular outflow tract pressure gradient (LVOTPG) only observed in HOCM group (P < 0.01). Ventricular tachycardia was seen in both groups. 28 out of 42 patients (66.67%) had misdiagnosis, and 4 out of 42 patients (9.53%) had losing diagnosis. Thus, coronary heart disease (CHD) had the highest rate of misdiagnosis. There were 20 CHD patients (71.43%) among 28 patients with misdiagnosis. Hypertension was in 3, congenital heart in 2, cerebro-embolism in 2, and myocarditis in 1. Conclusions For a patient with family history or sudden death history of HCM, unexplained syncope episodes, chest pain (angina), especially in young, an ejection murmur along the left sternum border, the presence of narrow and deep Q waves, or inversion of giant T waves in V3-V6, atrial fibrillation and /or cerebra-embolism echocardiogram should be given. CAG and LVG are necessary only if the result of echo is negative, and the patients with suspected HCM or CHD.     

Survival Implications: Hypertrophic Cardiomyopathy in Noonan Syndrome

Objectives. To understand relationships and survival implications between structural heart disease and hypertrophic cardiomyopathy in Noonan syndrome (Noonan syndrome‐HCM), we reviewed the clinical course of 138 children with Noonan syndrome diagnosed with cardiovascular abnormalities and compared survival with the 30 children with Noonan syndrome‐HCM with 120 contemporaneous children with nonsyndromic HCM. Methods. Study cohorts represent consecutive cases diagnosed at our institution 1966 through 2006. Outcomes were modeled using multiphase parametric techniques followed by multivariable regression with bagging. Results. Cardiac abnormalities in Noonan syndrome: Cardiac abnormalities in the 138 Noonan syndrome children included pulmonary valve dysplasia (52%), hypertrophic cardiomyopathy (22%), atrial septal defect (20%), ventricular septal defect (10%), mitral valve dysplasia (6%), coarctation (3%), and Fallot's tetralogy (2%). Need for surgery was high but not different from children with structural defects coexisting with HCM. Overall, late survival in children with Noonan syndrome and cardiac defects was good (91 ± 3% at 15 years), although significantly worse for those with Noonan syndrome‐HCM (P < .01). Noonan syndrome‐HCM vs. nonsyndromic HCM: In the 30 children with Noonan syndrome‐HCM, structural cardiac malformations coexisted in 18 (57%). The incidence of structural cardiac malformations in nonsyndromic HCM was instead 3/120 (2.5%, P < .001). Risk‐adjusted late survival was significantly worse for Noonan syndrome‐HCM than for nonsyndromic HCM (P= .02). Conclusions. Noonan syndrome‐HCM frequently coexists with structural cardiac malformations, whereas nonsyndromic HCM does not; their natural histories may therefore be different. Late survival is significantly worse for Noonan syndrome‐HCM than nonsyndromic HCM.     

MYH7基因Glu931del突变导致恶性肥厚型心肌病

目的 本研究拟查明1个中国汉族肥厚型心肌病（HCM）家系的致病突变,并探讨基因型-表型关联。方法 利用二代测序技术,全面筛查家系先证者的28个HCM相关致病基因。通过Sanger测序,在家系中验证和筛查发现的可能致病突变,并对突变携带者进行表型分析。结果 二代测序发现先证者携带MYH7基因Glu931del杂合突变。家系筛查发现4名患者均携带该突变,突变与疾病共分离,该突变为此HCM家系的致病突变,常染色体显性遗传。Glu931del突变位于MYH7基因第23外显子,三个核苷酸缺失（c.2791_2793del GAG）,导致其所编码的心脏β-肌球蛋白重链的第931位谷氨酸缺失。MYH7基因第931位谷氨酸残基在不同物种间高度保守。临床表型分析发现,家系中4例患者的左心室最厚厚度在19mm-30mm之间,静息状态均无明显左室流出道梗阻,表现为胸痛、心悸和呼吸困难,并伴黑曚或有晕厥史。该家系另有两例患者在家系筛查前发生猝死,确诊年龄分别为5岁和6岁,死亡年龄均为16岁。该家系随访12年,HCM临床症状进展较快,1例患者左心室最大厚度由7mm发展为30mm,两例患者心功能进展为NYHA分级Ⅲ/Ⅳ级。结论 MYH7基因Glu931del突变导致的HCM表型较严重,易发生猝死和心衰,但也存在较大的表型异质性。二代高通量测序可以用于HCM致病基因的全面筛查。     

Electrocardiographic Changes Announcing the Rapid Development of Apical Hypertrophic Cardiomyopathy in an Adult Male

We presented the case of an adult male without structural heart disease, who in the period of 3 years developed apical hypertrophic cardiomyopathy. ECG changes preceded the development of ventricular hypertrophy. We discussed the appearance of ventricular enlargement during adulthood, in some cases of hypertrophic cardiomyopathy (HC), and how the ECG abnormalities may precede the onset of ventricular hypertrophy.     

Hypertrophic Cardiomyopathy: Infants,Children, and Adolescents

Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate left ventricular hypertrophy (LVH) in the setting of a nondilated left ventricle. HCM is often associated with asymmetric LVH, a family history of HCM, sarcomeric genetic mutations, and an increased risk of sudden cardiac death. There is a wide clinical variability in HCM presenting during childhood and a relative lack of data on the pediatric population. This review will cover HCM presenting in infancy, childhood, and adolescence.