Referenced in: none

Automatically associated channels: Kv7.1 , Nav1.5

Title: A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome.

Authors: N Makita, N Shirai, M Nagashima, R Matsuoka, Y Yamada, N Tohse, A Kitabatake

Journal, date & volume: FEBS Lett., 1998 Feb 13 , 423, 5-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9506831

Abstract
Mutations in a human cardiac Na+ channel gene (SCN5A) are responsible for chromosome 3-linked congenital long QT syndrome (LQT3). Here we characterized a de novo missense mutation (R1623Q, S4 segment of domain 4) identified in an infant Japanese girl with a severe form of LQT3. When expressed in oocytes, mutant Na+ channels exhibited only minor abnormalities in channel activation, but in contrast to three previously characterized LQT3 mutations, had significantly delayed macroscopic inactivation. Single channel analysis revealed that R1623Q channels have significantly prolonged open times with bursting behavior, suggesting a novel mechanism of pathophysiology in Na+ channel-linked long QT syndrome.