RESUMO
BACKGROUND: Classic symptoms of long QT syndrome (LQTS) include prolongation of QT interval on electrocardiograph, syncope, and cardiac arrest due to a distinctive form of polymorphic ventricular tachycardia, known as Torsade de Pointes. We assessed occurrence of LQTS signs in individuals from 30 Czech families with mutations in KCNQ1 and KCNH2 genes. METHODS AND RESULTS: One hundred five individuals from 30 Czech families with LQTS were genotyped for KCNQ1 and KCNH2. The occurrence of typical LQTS signs (pathologic prolongation of QT interval; syncope; cardiac arrest; Torsade de Pointes) was clinically assessed by exercise test with QT interval analysis. Family history of sudden cardiac death was taken. Statistical analysis was performed to determine correlation of clinical results and mutation status. KCNQ1 gene mutations were found in 23 families, and KCNH2 gene mutations in eight families. Only 46 (70%) of the 66 mutation carriers had at least two of the typical LQTS signs. The others were minimally or asymptomatic. From 39 noncarrier individuals, only 1 fulfilled the clinical criteria of LQTS diagnosis, another 4 had an intermediate probability of diagnosis. The exercise test had 92% sensitivity and 93% specificity for LQTS diagnosis. CONCLUSIONS: Incidence of classical signs of LQTS was not high in Czech carriers of KCNQ1 and KCNH2 mutations. Therefore, proper diagnosis relies on detection of symptoms at presentation. The exercise test may be beneficial owing to its high sensitivity and specificity for LQTS diagnosis.
Assuntos
Eletrocardiografia/estatística & dados numéricos , Canais de Potássio Éter-A-Go-Go/genética , Teste de Esforço/estatística & dados numéricos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/genética , RNA Longo não Codificante/genética , Adulto , República Tcheca/epidemiologia , Canal de Potássio ERG1 , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Síndrome do QT Longo/epidemiologia , Masculino , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Prevalência , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Observations from population-based studies demonstrated a strong genetic component of sudden cardiac death. The aim of this study was to test the hypothesis that ion channel genes mutations are more common in ventricular fibrillation (VF) survivors with coronary artery disease (CAD) compared to controls. METHODS: The entire coding sequence of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes was analyzed in 45 (five females) CAD individuals-survivors of documented VF and in 90 matched healthy controls. In another control group of 141 matched patients with CAD without malignant arrhythmias, the exons containing rare coding variants found in the VF survivors were sequenced. RESULTS: The carrier frequency of all the rare sequence variants was significantly higher in the VF survivors (8/45, 17.8%) than in CAD controls (3/141, 2.2%, P = 0.001). In VF survivors, four coding variants in eight individuals were found. Three in KCNH2 gene: R148W and GAG186del are novel; P347S was previously related to long QT syndrome. In SCN5A gene, P2006A variant was found in five unrelated males. This variant has been demonstrated previously to have small effect on sodium channel kinetics. No rare coding variants were found in the healthy controls. The P2006A variant was found in three CAD controls. CONCLUSION: The prevalence of selected, rare coding variants in five long QT genes was significantly higher in cases versus controls, confirming a mechanistic role for these genes among a subgroup of patients with coronary disease and VF.
Assuntos
Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/mortalidade , Polimorfismo de Nucleotídeo Único/genética , Canais de Potássio/genética , Fibrilação Ventricular/genética , Fibrilação Ventricular/mortalidade , Idoso , Comorbidade , República Tcheca/epidemiologia , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , SobreviventesRESUMO
In a 7-year-old boy with normal hearing suffering from repeated syncope an extremely prolonged QTc interval (up to 700 ms) was found. The mother was completely asymptomatic and the father had an intermittently borderline QTc interval (maximum 470 ms) but no symptoms. In the proband a mutation analysis of KCNQ1 gene revealed a homozygous 1893insC mutation. The parents were heterozygous for this mutation. There was no consanguineous marriage in the family. The clinical relevance of these findings is that apparently normal individuals may have a latent reduction of repolarizing currents, a "reduced repolarization reserve," because they are carriers of latent ion channel genes mutations.