新生儿先天性肥厚性心肌病一例报道

新生儿先天性肥厚心肌病是很少见的一种先天性心脏病,现将我科诊治的1例报告如下.     

肥厚性心肌病基因调控新进展

随着分子遗传学的飞速发展 ,人们对肥厚性心肌病的基因调控的认识也在不断提高。至今 ,已经发现七种主要的基因突变可以导致该病 ,基因型和表型关系的研究也在深入 ,对该病基因水平的研究必将引起临床治疗的进步。本文综述了肥厚性心肌病遗传学研究的新进展     

肥厚性心肌病相关基因的研究进展

肥厚性心肌病(hypertrophic cardiomyopathy,HCM)是以左心室或室间隔不对称性肥厚为基本特征的原发性心肌病,其发病率约为0.2％,是青少年和运动员心源性猝死的首要原因,目前被普遍认为是一种基因突变所致的常染色体显性遗传性疾病.至今为止,至少有20种基因的450余种突变被报道与HCM相关,主要定位于心脏肌节蛋白基因.此外越来越多的线粒体基因、修饰基因突变也被发现与HCM的发生发展有关.该文将对HCM的相关基因的研究进展作一个综述.     

肥厚性心肌病的分子基础与临床意义

肥厚性心肌病是一种遗传异质性疾病。第一个肥厚性心肌病因位点于１９８９年定位于第１４号染色体长臂的β型肌球蛋白重链基因，迄今已有３０多个点突变和一个缺失突变被发现。带突变的ｍＲＮＡ和蛋白质表达在肥厚性心肌病病人的心肌和骨骼肌。除β型肌球蛋白重链基因外，最近又有３个基因位点被发现。分别位于第１、１１和１５号染色体的长臂，其确切基因尚在探索中，临床分析表明，某些基因突变与心脏猝死的高发率有关。筛查基因突     

微血管密度在肥厚性心肌病合并房颤患者中的变化特点及其影响

目的:探讨微血管密度在肥厚性心肌病患者中的变化特点及意义。方法:选取2016年3月至2019年10月间在新乡医学院附属南阳市第二人民医院就诊的肥厚性心肌病患者46例,分为合并房颤组11例,未合并房颤组35例。心脏核磁共振成像测量左室舒张末期内径、质量指数、容量指数,以及左心房内径、左室射血分数、室间隔厚度。取患者外科手...     

心尖肥厚性心肌病心电图与临床分析

心尖肥厚性心肌病(AHCM)是肥厚性心肌病的一种亚型,属原发性心肌病.其于1976年由日本学者首先报道,占肥厚性心肌病的2%-24%,病因不明.其以心尖部及其附近心肌肥厚及心肌纤维排列紊乱为特征,常不伴左室流出道梗阻和压力阶差.心源性猝死是其最严重的并发症.2005年2月至2009年12月,我院共收治34例AHCM患者,现对其心电图特征进行回顾性分析,旨在为临床诊治提供依据.     

应激性心肌病的发病机理

应激性心肌病指那些非冠状动脉狭窄或堵塞，因强烈刺激使机体释放大量儿茶酚胺所造成的心肌损伤，甚至导致致死性心律紊乱而突然死亡的病例。本文对有关机理作一综述。     

造影超声心动图评价肥厚型心肌病左室下壁肥厚的应用价值

本研究旨在探讨造影超声心动图(CEcho)评价肥厚型心肌病(HCM)左室下壁肥厚的价值。选取2015年5月至2016年10月在四川大学华西医院诊断的HCM患者114例,均行常规超声心动图(Echo)和CEcho检查,其中45例行心脏磁共振检查(CMR),47例行动态心电图(Holter)检查。分析HCM患者中左室下壁肥厚发生的频次及其所占的比例,并进一步探索HCM伴下壁肥厚患者心脏结构及功能变化。结果显示:(1)CEcho对HCM患者下壁肥厚的检出率为60%,较Echo检出率(48%)明显增高。(2)与金标准CMR对比,CEcho测量下壁基底段及中段舒张及收缩末期厚度无明显差异,但有增高的趋势;Echo测值低于CMR(P<0.05)及CEcho(P<0.05)。(3)Bland-Altman分析显示,CEcho与CMR测量下壁厚度的一致性较好。和Echo与CMR测量下壁厚度的结果相比,CEcho与CMR测量下壁厚度差值的95%一致性界限(CI)较小。回归分析显示CEcho与CMR测量下壁厚度的拟合度较好。(4)Holter结果显示下壁肥厚患者出现室性早搏≥500次/24 h的概率大于下壁非肥厚患者。结果表明CEcho可以较敏感地检出左室下壁肥厚,而Echo可能低估左室下壁厚度。HCM伴下壁肥厚患者发生室性早搏事件的可能性有所增加。     

Novel insights on GTPBP3-associated hypertrophic cardiomyopathy

About 100 genes have been associated with cardiomyopathies with genotype–phenotype correlations often hard to establish. Genetic testing may help to confirm the genetic diagnosis and assess the risk of inheritance in the family. A 25-year old male with hypertrophic cardiomyopathy and fasciculoventricular accessory pathway was referred for genetic testing by his cardiologist. Targeted PRKAG2 screening and whole-exome sequencing were performed, followed by Sanger sequencing segregation analysis in the family. The PRKAG2 gene screening was negative. Whole-exome sequencing revealed the following four variants in the patient: c.181G>C (p.Ala61Pro) and c.1199C>T (p.Thr400Met) in the GTPBP3 gene, as well as c.752C>T (p.Thr251Ile) and c.1760C>T (p.Pro587Leu) in the POLG gene. Family segregation analysis showed that the patient's mother is a carrier of variant c.181G>C and the patient's paternal grandmother is a carrier of variant c.1199C>T in the GTPBP3 gene, which is in accordance with an autosomal recessive model of inheritance of the disease. Both variants in the POLG are found paternally inherited in the patient's healthy half-brother, thus are not considered disease-causing. GTPBP3 variants have been reported in patients with hypertrophic cardiomyopathy, associated with combined oxidative phosphorylation deficiency 23. These novel variants represent the probable cause of the observed clinical symptoms in the patient.     

Genetics of feline hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is characterized by an abnormal increase in myocardial mass that affects cardiac structure and function. HCM is the most common inherited cardiovascular disease in humans (0.2%) and the most common cardiovascular disease in cats (14.7%). Feline HCM phenotype is very similar to the phenotype found in humans, but the time frame for the development of the disease is significantly shorter. Similar therapeutic agents are used in its treatment and it has the same complications, such as heart failure, thromboembolism and sudden cardiac death. In contrast to humans, in whom thousands of genetic variants have been identified, genetic studies in cats have been limited to fragment analysis of two sarcomeric genes identifying two variants in MYBPC3 and one in MYH7. Two of these variants have also been associated with human disease. The high prevalence of the reported variants in non-affected cats hinders the assumption of their pathogenicity in heterozygotes. An in-depth review of the literature about genetic studies on feline HCM in comparison with the same disease in humans is presented here. The close similarity in the phenotype and genotype between cats and humans makes the cat an excellent model for the pathophysiological study of the disease and future therapeutic agents.     

Pathological analysis of hypertrophic cardiomyopathy simulating dilated cardiomyopathy

The pathomorphologic features of hypertrophic cardiomyopathy simulating dilated cardiomyopathy in the late stage (HCM-DCM) were compared with those of ordinary hypertrophic cardiomyopathy (HCM). Seven autopsied hearts with HCM-DCM and 11 with HCM were assessed quantitatively using an image analyzer. Unlike HCM, significant left ventricular enlargement and wall thinning were observed in HCM-DCM, and the percentage areas of massive fibrosis and disarray were significantly greater. In HCM-DCM, the disarray was distributed diffusely, whereas massive fibrosis was distributed more intensively in the ventricular septum and anterior wall than in the lateral and posterior wall. Narrowing of intramyocardial small arteries was observed more frequently in HCM-DCM, especially in the ventricular septum and anterior wall, than in HCM. These results suggest that the enlargement and wall thinning of the left ventricle in HCM-DCM are attributable to non-uniform progression of massive fibrosis, which is closely related to small-arterial lesions.     

The role of renin-angiotensin-aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

The phenotypic variability of hypertrophic cardiomyopathy (HCM) in patients with identical pathogenic mutations suggests additional modifiers. In view of the regulatory role in cardiac function, blood pressure, and electrolyte homeostasis, polymorphisms in the renin-angiotensin-aldosterone system (RAAS) are candidates for modifying phenotypic expression. In order to investigate whether RAAS polymorphisms modulate HCM phenotype, we selected a large cohort of carriers of one of the three functionally equivalent truncating mutations in the MYBPC3 gene. Family-based association analysis was performed to analyze the effects of five candidate RAAS polymorphisms (ACE, rs4646994; AGTR1, rs5186; CMA, rs1800875; AGT, rs699; CYP11B2, rs1799998) in 368 subjects carrying one of the three mutations in the MYBPC3 gene. Interventricular septum (IVS) thickness and Wigle score were assessed by 2D-echocardiography. SNPs in the RAAS system were analyzed separately and combined as a pro-left ventricular hypertrophy (LVH) score for effects on the HCM phenotype. Analyzing the five polymorphisms separately for effects on IVS thickness and Wigle score detected two modest associations. Carriers of the CC genotype in the AGT gene had less pronounced IVS thickness compared with CT and TT genotype carriers. The DD polymorphism in the ACE gene was associated with a high Wigle score (P=0.01). No association was detected between the pro-LVH score and IVS thickness or Wigle score. In conclusion, in contrast to previous studies, in our large study population of HCM patients with functionally equivalent mutations in the MYBPC3 gene we did not find major effects of genetic variation within the genes of the RAAS system on phenotypic expression of HCM.     

Genetics of hypertrophic cardiomyopathy in Norway

Genetic testing for hypertrophic cardiomyopathy (HCM) became available in Norway in 2003. Here, we describe the results of this testing in probands with HCM referred until the end of 2012. The translated exons of MYBPC3, MYH7, TNNI3, TNNT2, MYL2 and MYL3 were analyzed in two groups of probands. In Group 1, comprising 696 probands above 1 year of age, a mutation was found in 203 patients (29.2%). Of those, 5.9% were carriers of two mutations. Mean age in double mutation carriers, single mutation carriers and mutation negative probands was 44 years (±19 years), 50 years (±15 years) and 55 years (±16 years), respectively. In Group 2, comprising 26 infants below the age of 1, a mutation was found in 15.4%. A total of 120 different mutations were found of which 51 (42.5%) were novel.     

The role of human urotensin-II in patients with hypertrophic cardiomyopathy

Objective: Hypertrophic cardiomyopathy (HCM) is a genetic condition with the hallmark feature of left ventricular hypertrophy. Human Urotensin-II (hUT-II) is regarded as a cardiovascular autacoid/hormone, and it has cardiac inotropic and hypertrophic properties. Aims of this study were to elucidate the clinical significance of serum hUT-II levels as a potential new biomarker in patients with HCM.

Methods: This study included 40 HCM patients (60% males and 40% females) and were compared to 30 healthy control subjects (47% males and 53% females. All patients underwent extensive clinical, laboratory, and echocardiographic. Blood samples were taken to test for serum hUT-II levels by commercial ELISA Kit.

Results: Serum hUT-II was significantly higher (p < 0.01) in patients with HCM (15.8 ± 2.1 pmol/L) compared with healthy controls (3.3 ± 1.7 pmol/L). With regard to HCM patient, Serum hUT-II levels were significantly higher in the female with 16.3 ± 1.9 pmol/L than the male with 15.4 ± 2.2 pmol/L (p < 0.05). Among echocardiographic parameters, hUT-II was negatively associated with ejection fraction (r = -0.160, p = 0.324).

Conclusion: Results of the first study indicated that serum hUT-II levels were markedly elevated in patients with HCM. Serum hUT-II is a novel biomarker parameter that has clinical use in patients with the severity of LVH.     

The pathology of hypertrophic cardiomyopathy

Sudden cardiac death (SCD) is devastating at any age, but even more so when the individual affected is young and asymptomatic, and the death is entirely unexpected. SCD is a catastrophic complication of hypertrophic cardiomyopathy (HCM) and may be the first manifestation of this disease. HCM is an inherited intrinsic disease of the myocardium characterized by left ventricular hypertrophy without chamber dilatation, in the absence of either a systemic or other cardiac disease, which may cause a similar magnitude of hypertrophy. HCM may be a clinically silent disease. Indeed, the pathologist may be the first to encounter a case of HCM at autopsy. HCM has wide-ranging implications for affected families, who will require cardiac screening and genetic counselling even if mutations are not known. Therefore, prompt and accurate diagnosis of HCM is vital. This review article will focus on the pathological diagnosis of HCM, recent advances in the genetics of this disease, and common pitfalls which may arise, leading to diagnostic uncertainty.     

Phenotypic spectrum of ALPK3‐related cardiomyopathy

Cardiomyopathies are clinically heterogeneous disorders and are the leading cause of cardiovascular morbidity and mortality. Different etiologies have a significant impact on prognosis. Recently, novel biallelic loss‐of‐function pathogenic variants in alpha‐kinase 3 (ALPK3) were implicated in causing early‐onset pediatric cardiomyopathy (cardiomyopathy, familial hypertrophic 27; OMIM 618052). To date, eight patients, all presented during early childhood, were reported with biallelic ALPK3 pathogenic variants. We describe the molecular and clinical phenotype characterization of familial cardiomyopathy on one family with six affected individuals. We identified homozygosity for an ALPK3 deleterious sequence variant (NM_020778.4:c.639G>A:p.Trp213*) in all the affected individuals. They presented with either dilated cardiomyopathy that progressed to hypertrophic cardiomyopathy (HCM) or HCM with left ventricular noncompaction. The age of presentation in our cohort extends between infancy to the fourth decade. The phenotypic severity decreases with the progression of age.     

β-肌球蛋白重链基因与肥厚型心肌病临床表型关系的研究

目的 研究肥厚型心肌病(hypertrophic cardiomyopathy,HCM)的主要致病基因β-肌球蛋白重链基因(beta-myosin heavy chin gene,MYH7)的突变位点,探寻基因型与表型的关系.方法 扩增3个HCM家系成员的MyH7基因第3、5、7～9、11～16、18～23外显子序列,进行直接测序分析,应用软件与标准序列比对,确定可能的突变位点.结果 发现其中1个家系MYH7基因第14外显子存在Thr441Met 突变,正常对照组相同位置未见异常.3个家系均发现多个同义突变位点.结论 在中国汉族人群中发现MYH2基因Thr441Met突变,该突变位于β-肌球蛋白重链头部肌动蛋白结合位点,可能是HCM的致病突变.HCM具有遗传异质性,多种因素可能参与其发生和发展过程.     

Anti-calreticulin antibodies and calreticulin in sera of patients diagnosed with dilated or hypertrophic cardiomyopathy

Distinct cellular level of the Ca²⁺-binding chaperone calreticulin (CRT) is essential for correct embryonal cardiac development and postnatal function. However, CRT is also a potential autoantigen eliciting formation of antibodies (Ab), whose role is not yet clarified. Immunization with CRT leads to cardiac injury, while overexpression of CRT in cardiomyocytes induces dilated cardiomyopathy (DCM) in animals. Hence, we analysed levels of anti-CRT Ab and calreticulin in the sera of patients with idiopatic DCM and hypertrophic cardiomyopathy (HCM). ELISA and immunoblot using human recombinant CRT and Pepscan with synthetic, overlapping decapeptides of CRT were used to detect anti-CRT Ab. Serum CRT concentration was tested by ELISA. Significantly increased levels of anti-CRT Ab of isotypes IgA (p?p?p?相似文献