Molecular characterization of two founder mutations causing long QT syndrome and identification of compound heterozygous patients.

Détails

ID Serval
serval:BIB_30AD4032C81A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Molecular characterization of two founder mutations causing long QT syndrome and identification of compound heterozygous patients.
Périodique
Annals of Medicine
Auteur(s)
Fodstad H., Bendahhou S., Rougier J.S., Laitinen-Forsblom P.J., Barhanin J., Abriel H., Schild L., Kontula K., Swan H.
ISSN
0785-3890
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
38
Numéro
4
Pages
294-304
Langue
anglais
Résumé
BACKGROUND: Mutations of at least six different genes have been found to cause long QT syndrome (LQTS), an inherited arrhythmic disorder characterized by a prolonged QT interval on the electrocardiogram (ECG), ventricular arrhythmias and risk of sudden death. AIM: The aims were to define the yet undetermined phenotypic characteristics of two founder mutations and to study clinical features in compound heterozygotes identified during the course of the study. METHODS: To maximize identification of the compound heterozygotes, we used an extended group of LQTS patients comprising 700 documented or suspected cases. Functional studies were carried out upon transient expression in COS-7 or HEK293 cells. RESULTS: The KCNQ1 IVS7-2A>G (KCNQ1-FinB) mutation associated with a mean QTc interval of 464 ms and a complete loss-of-channel function. The HERG R176W (HERG-FinB) mutation caused a reduction in current density as well as slight acceleration of the deactivation kinetics in vitro, and its carriers had a mean QTc of 448 ms. The HERG R176W mutation was also present in 3 (0.9%) out of 317 blood donors. A total of six compound heterozygotes were identified who had the HERG R176W mutation in combination with a previously reported LQTS mutation (KCNQ1 G589D or IVS7-2A>G). When present simultaneously with an apparent LQTS-causing mutation, the HERG R176W mutation may exert an additional in vivo phenotypic effect. CONCLUSIONS: The HERG R176W mutation represents a population-prevalent mutation predisposing to LQTS. Compound heterozygosity for mutant LQTS genes may modify the clinical picture in LQTS.
Mots-clé
Adult, Animals, COS Cells, Cercopithecus aethiops, Child, Preschool, Ether-A-Go-Go Potassium Channels, Female, Finland, Heterozygote, Heterozygote Detection, Humans, KCNQ1 Potassium Channel, Long QT Syndrome, Male, Membrane Potentials, Muscle Proteins, Mutation, Sodium Channels, Transfection
Pubmed
Web of science
Création de la notice
24/01/2008 11:56
Dernière modification de la notice
20/08/2019 14:15
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