Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inherited heart disease causing electric instability in the heart has been suggested to be a risk factor for sudden unexpected death in epilepsy (SUDEP). The purpose of this study was to reveal the correlation between epilepsy-related sudden unexpected death (SUD) and inherited heart disease. Twelve epilepsy-related SUD cases (seven males and five females, aged 11-78 years) were examined. Nine cases fulfilled the criteria of SUDEP, and three cases died by drowning. In addition to examining three major epilepsy-related genes, we used next-generation sequencing (NGS) to examine 73 inherited heart disease-related genes. We detected both known pathogenic variants and rare variants with minor allele frequencies of <0.5%. The pathogenicity of these variants was evaluated and graded by eight in silico predictive algorithms. Six known and six potential rare variants were detected. Among these, three known variants of LDB3, DSC2 and KCNE1 and three potential rare variants of MYH6, DSP and DSG2 were predicted by in silico analysis as possibly highly pathogenic in three of the nine SUDEP cases. Two of three cases with desmosome-related variants showed mild but possible significant right ventricular dysplasia-like pathology. A case with LDB3 and MYH6 variants showed hypertrabeculation of the left ventricle and severe fibrosis of the cardiac conduction system. In the three drowning death cases, one case with mild prolonged QT interval had two variants in ANK2. This study shows that inherited heart disease may be a significant risk factor for SUD in some epilepsy cases, even if pathological findings of the heart had not progressed to an advanced stage of the disease. A combination of detailed pathological examination of the heart and gene analysis using NGS may be useful for evaluating arrhythmogenic potential of epilepsy-related SUD.
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PMID:Epilepsy-related sudden unexpected death: targeted molecular analysis of inherited heart disease genes using next-generation DNA sequencing. 2713 74

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is induced by emotions or exercise in patients without organic heart disease and may be polymorphic or bidirectional in nature. The prognosis of CPVT is not good, and therefore prevention of sudden death is of utmost importance. Genetic variants of CPVT include RyR2, CASQ2, CALM2, TRD, and possibly KCNJ2 and ANK2 gene mutations. Hypotheses that suggest the causes of CPVT include weakened binding of FKBP12.6 and RyR2, a store overload-induced Ca2+ release (SOICR), unzipping of intramolecular domain interactions in RyR2, and molecular and functional abnormalities caused by mutations in the CASQ2 gene. The incidence of an RyR2 anomaly in CPVTs is about 35-79%, whereas anomalies in the CASQ2 gene account for 3-5% CPVTs. The ping-pong theory, suggesting that reciprocating delayed after depolarization induces bigeminy of the right and left bundle branches, may explain the pathogenesis of bidirectional ventricular tachycardia. Flecainide, carvedilol, left sympathetic nerve denervation, and catheter ablation of the PVC may serve as new therapeutic strategies for CPVT while gene-therapy may be applied to some types of CPVT in the future. Although, not all sudden cardiac deaths in CPVT patients are currently preventable, new medical and interventional therapies may improve CPVT prognosis.
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PMID:Current topics in catecholaminergic polymorphic ventricular tachycardia. 2776 Nov 57