KCNJ2 mutations in arrhythmia patients referred for LQT testing: a mutation T305A with novel effect on rectification properties.

Background: Loss-of-function mutations in the KCNJ2 cause approximately 50% of Andersen-Tawil Syndrome (ATS) characterized by a classic triad of periodic paralysis, ventricular arrhythmia, and dysmorphic features. Do KCNJ2 mutations occur in patients lacking this triad and lacking a family history of ATS?

Objectives: The purpose of this study was to identify and characterize mutations in the KCNJ2-encoded inward rectifier potassium channel Kir2.1 from patients referred for genetic arrhythmia testing.

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.

Na(+) current in human ventricle: implications for sodium loading and homeostasis.

The Na current (I(Na)) in human ventricle is carried through a specific isoform of the voltage gated Na channel in heart. The pore forming alpha-subunit is encoded by the gene SCN5A. Up to four beta-subunits may be associated, and the larger macromolecular complex may include attachments to cytoskeleton and scaffolding proteins, all of which may affect the gating kinetics of the current.