Identification of Kv11.1 isoform switch as a novel pathogenic mechanism of long-QT syndrome.

ABSTRACT:

Background

The KCNH2 gene encodes the Kv11.1 potassium channel that conducts the rapidly activating delayed rectifier current in the heart. The relative expression of the full-length Kv11.1a isoform and the C-terminally truncated Kv11.1a-USO isoform plays an important role in regulation of channel function. The formation of C-terminal isoforms is determined by competition between the splicing and alternative polyadenylation of KCNH2 intron 9. It is not known whether changes in the relative expression of Kv11.1a and Kv11.1a-USO can cause long-QT syndrome.

Methods and results

We identified a novel KCNH2 splice site mutation in a large family. The mutation, IVS9-2delA, is a deletion of the A in the AG dinucleotide of the 3' acceptor site of intron 9. We designed an intron-conta

SUBMITTER: Gong Q 

PROVIDER: S-EPMC4180443 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature