Cardiac channel molecular autopsy: insights from 173 consecutive cases of autopsy-negative sudden unexplained death referred for postmortem genetic testing.

Objective: To perform long QT syndrome and catecholaminergic polymorphic ventricular tachycardia cardiac channel postmortem genetic testing (molecular autopsy) for a large cohort of cases of autopsy-negative sudden unexplained death (SUD).

Methods: From September 1, 1998, through October 31, 2010, 173 cases of SUD (106 males; mean ± SD age, 18.4 ± 12.

Implantable cardioverter defibrillator therapy for congenital long QT syndrome: a single-center experience.

Background: Long QT syndrome's (LQTS) marked heterogeneity necessitates both evidence-based and individualized therapeutic approaches.

Objective: This study sought to analyze a single LQTS specialty center's experience regarding the relationship between risk factors and appropriate ventricular fibrillation (VF)-terminating therapies among LQTS patients treated with an implantable cardioverter-defibrillator (ICD).

Methods: An internal review board-approved, retrospective analysis of the electronic medical records of 459 patients with genetically confirmed LQTS including the 51 patients (14 LQT1, 22 LQT2, and 15 LQT3) who received an ICD from 2000 to 2010 was performed.

Diagnostic miscues in congenital long-QT syndrome.

Background: Long-QT syndrome (LQTS) is a potentially lethal cardiac channelopathy that can be mistaken for palpitations, neurocardiogenic syncope, and epilepsy. Because of increased physician and public awareness of warning signs suggestive of LQTS, there is the potential for LQTS to be overdiagnosed. We sought to determine the agreement between the dismissal diagnosis from an LQTS subspecialty clinic and the original referral diagnosis.

Genotypic heterogeneity and phenotypic mimicry among unrelated patients referred for catecholaminergic polymorphic ventricular tachycardia genetic testing.

Background: Mutations in the RyR2-encoded cardiac ryanodine receptor/calcium release channel and in CASQ2-encoded calsequestrin cause catecholaminergic polymorphic ventricular tachycardia (CPVT1 and CPVT2, respectively).

Objectives: The purpose of this study was to evaluate the extent of genotypic and phenotypic heterogeneity among referrals for CPVT genetic testing.

Methods: Using denaturing high-performance liquid chromatography and DNA sequencing, mutational analysis of 23 RyR2 exons previously implicated in CPVT1, comprehensive analysis of all translated exons in CASQ2 (CPVT2), KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), KCNE2 (LQT6), and KCNJ2 (Andersen-Tawil syndrome [ATS1], also annotated LQT7), and analysis of 10 ANK2 exons implicated in LQT4 were performed on genomic DNA from 11 unrelated patients (8 females) referred to Mayo Clinic's Sudden Death Genomics Laboratory explicitly for CPVT genetic testing.

Effect of clinical phenotype on yield of long QT syndrome genetic testing.

Objectives: The purpose of this study was to examine the effect of clinical phenotype on the yield of genetic testing for congenital long QT syndrome (LQTS).

Background: Since the discovery of the first LQTS susceptibility genes in 1995, numerous genotype-phenotype relationships have emerged during the past decade of research genetic testing. In May 2004, LQTS genetic testing became a clinically available molecular diagnostic test.

Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

Objectives: The purpose of this study was to determine the spectrum and prevalence of cardiac channel mutations among a large cohort of consecutive, unrelated patients referred for long QT syndrome (LQTS) genetic testing.

Background: Congenital LQTS is a primary cardiac channelopathy. More than 300 mutations have been identified in five genes encoding key ion channel subunits.

Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes.

Background: Swimming is a relatively genotype-specific arrhythmogenic trigger for type 1 long-QT syndrome (LQT1). We hypothesize that mimickers of concealed LQT1, namely catecholaminergic polymorphic ventricular tachycardia (CPVT), may also underlie swimming-triggered cardiac events.

Methods And Results: Between August 1997 and May 2003, 388 consecutive, unrelated patients were referred specifically for LQTS genetic testing.