scholarly journals GW26-e4658 Study on the Molecular Genetic between Hypertrophic Cardiomyopathy and FKBP12.6

2015 ◽  
Vol 66 (16) ◽  
pp. C80
Author(s):  
Zhicheng Xu ◽  
Qiongqiong Zhou ◽  
Yang Shen ◽  
Linjuan Guo ◽  
Jiejing Jin ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Molecular Genetic

Differences in the diagnostic value of various criteria of negative T waves for hypertrophic cardiomyopathy based on a molecular genetic diagnosis

2007 ◽  
Vol 112 (11) ◽  
pp. 577-582 ◽  
Author(s):  
Tetsuo Konno ◽  
Noboru Fujino ◽  
Kenshi Hayashi ◽  
Katsuharu Uchiyama ◽  
Eiichi Masuta ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Diagnostic Value ◽  
Left Ventricular ◽  
Lower Sensitivity ◽  
T Wave ◽  
Accurate Definition ◽  
Definition Of ◽  
T Waves

Differences in the diagnostic value of a variety of definitions of negative T waves for HCM (hypertrophic cardiomyopathy) have not yet been clarified, resulting in a number of definitions being applied in previous studies. The aim of the present study was to determine the most accurate diagnostic definition of negative T waves for HCM in genotyped populations. Electrocardiographic and echocardiographic findings were analysed in 161 genotyped subjects (97 carriers and 64 non-carriers). We applied three different criteria that have been used in previous studies: Criterion 1, negative T wave >10 mm in depth in any leads; Criterion 2, negative T wave >3 mm in depth in at least two leads; and Criterion 3, negative T wave >1 mm in depth in at least two leads. Of the three criteria, Criterion 3 had the highest sensitivity (43% compared with 5 and 26% in Criterion 1 and Criterion 2 respectively; P<0.0001) and retained a specificity of 95%, resulting in the highest accuracy. In comparison with abnormal Q waves, negative T waves for Criterion 3 had a lower sensitivity in detecting carriers without LVH (left ventricular hypertrophy) (12.9% for negative T waves compared with 22.6% for abnormal Q waves). On the other hand, in detecting carriers with LVH, the sensitivity of negative T waves increased in a stepwise direction with the increasing extent of LVH (P<0.001), whereas there was less association between the sensitivity of abnormal Q waves and the extent of LVH. In conclusion, Criterion 3 for negative T waves may be the most accurate definition of HCM based on genetic diagnoses. Negative T waves may show different diagnostic value according to the different criteria and phenotypes in genotyped populations with HCM.

scholarly journals Genetic Testing in Patients with Hypertrophic Cardiomyopathy

2021 ◽  
Vol 22 (19) ◽  
pp. 10401
Author(s):  
Jiri Bonaventura ◽  
Eva Polakova ◽  
Veronika Vejtasova ◽  
Josef Veselka
Keyword(s):  
Genetic Testing ◽  
Hypertrophic Cardiomyopathy ◽  
Genetic Basis ◽  
Molecular Genetic ◽  
Mendelian Disease ◽  
Sarcomeric Proteins ◽  
Pathogenic Variants ◽  
Large Numbers ◽  
Uncertain Significance ◽  
Common Clinical Practice

Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with an estimated prevalence of up to 1 in 200 individuals. In the majority of cases, HCM is considered a Mendelian disease, with mainly autosomal dominant inheritance. Most pathogenic variants are usually detected in genes for sarcomeric proteins. Nowadays, the genetic basis of HCM is believed to be rather complex. Thousands of mutations in more than 60 genes have been described in association with HCM. Nevertheless, screening large numbers of genes results in the identification of many genetic variants of uncertain significance and makes the interpretation of the results difficult. Patients lacking a pathogenic variant are now believed to have non-Mendelian HCM and probably have a better prognosis than patients with sarcomeric pathogenic mutations. Identifying the genetic basis of HCM creates remarkable opportunities to understand how the disease develops, and by extension, how to disrupt the disease progression in the future. The aim of this review is to discuss the brief history and recent advances in the genetics of HCM and the application of molecular genetic testing into common clinical practice.

scholarly journals Rapid molecular genetic diagnosis of hypertrophic cardiomyopathy by semiconductor sequencing

2014 ◽  
Vol 12 (1) ◽  
pp. 173 ◽  
Author(s):  
Zongzhe Li ◽  
Jin Huang ◽  
Jinzhao Zhao ◽  
Chen Chen ◽  
Hong Wang ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Semiconductor Sequencing ◽  
Molecular Genetic Diagnosis

Abstract 58: Modeling Pathogenesis in Familial Hypertrophic Cardiomyopathy Using Patient-Specific Induced Pluripotent Stem Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Feng lan ◽  
Andrew Lee ◽  
Ping Liang ◽  
Enrique Navarrete ◽  
Li Wang ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Molecular Genetic ◽  
Dermal Fibroblasts ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Patient Specific ◽  
Activated T Cells ◽  
Cellular Hypertrophy ◽  
Induced Pluripotent

Background: Hypertrophic cardiomyopathy (HCM) is a prevalent familial cardiac disorder linked to development of heart failure, arrhythmia, and sudden cardiac death. Molecular genetic studies have demonstrated HCM is caused by mutations in genes encoding for the cardiac sarcomere. However, the pathways by which sarcomeric mutations result in myocyte hypertrophy and contractile abnormalities are not well understood. Methods: We aimed to elucidate the molecular mechanisms underlying the development of HCM through the generation of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from dermal fibroblasts of a 10 member family, five of whom carry a hereditary HCM missense mutation (Arg663His) in the MYH7 gene. Results: As compared to control iPSC-CMs derived from healthy family members, HCM iPSC-CMs exhibited enlarged cell size, increased atrial natriuretic factor (ANF) expression, nuclear translocation of nuclear factor of activated T-cells (NFAT), and aggravated contractile dysfunction in response to stimulation by β-adrenergic agonists. Interestingly, both video analysis of beating cells and whole cell patch clamping revealed arrhythmia in a significant portion of diseased iPSC-CMs at the single cell level. Ca 2+ imaging demonstrated elevated cytoplasmic Ca 2+ content and irregular transients in HCM iPSC-CMs prior to the onset of cellular hypertrophy, suggesting the HCM phenotype is triggered by dysfunction in Ca 2+ cycling. Treatment of irregular Ca 2+ homeostasis by the Ca 2+ channel blocker verapamil prevented development of cellular hypertrophy and arrhythmia. Conclusions: We hypothesize the cellular abnormalities observed in HCM iPSC-CMs are caused by deficiencies in Ca 2+ regulation. We anticipate our findings will elucidate the mechanisms underlying HCM development and identify novel targets for treatment of the disease.

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