Referenced in: none

Automatically associated channels: Kv11.1 , Kv7.1 , Nav1.5

Title: Identification of a new SCN5A mutation, D1840G, associated with the long QT syndrome. Mutations in brief no. 153. Online.

Authors: J Benhorin, M Goldmit, J W MacCluer, J Blangero, R Goffen, A Leibovitch, A Rahat, Q Wang, A Medina, J Towbin, B Kerem

Journal, date & volume: Hum. Mutat., 1998 , 12, 72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/10627139

Abstract
The long QT syndrome (LQT) is an inherited cardiac disorder that can cause sudden cardiac death among apparently healthy young individuals due to malignant ventricular arrhythmias. LQT was found to be caused by mutations in four genes LTQ1, LQT2, LQT3 and LQT5, and linkage was reported for an additional locus, LQT4, on chromosome 4q25-27. We have studied a large (n=131) LQT-affected Jewish kindred and identified tight linkage between the LQT-affected status and LQT3 (lod score 6.13, with an estimated recombination fraction of zero). We identified a new point-mutation, A to G substitution at nucleotide 5519 of the SCN5A gene, changing the aspartate 1840 to glycine, D1840G. This is a non-conservative change of an amino acid completely conserved in sodium channels from Molusca to human. The mutation was identified in all affected individuals (n=23), and not identified in all the unaffected family members (n=40), and not in 200 chromosomes of healthy control individuals. The mutation was identified in 3/12 individuals with equivocal phenotype, thus, providing an accurate dignostic tool for all family members. This mutation is currently being used in a cellular electrophysiological model, to characterize the function of the mutated sodium channel in this syndrome.