Molecular characterization of two founder mutations causing long QT syndrome and identification of compound heterozygous patients.
Ann Med
; 38(4): 294-304, 2006.
Article
em En
| MEDLINE
| ID: mdl-16754261
ABSTRACT
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.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Síndrome do QT Longo
/
Canal de Potássio KCNQ1
/
Canais de Potássio Éter-A-Go-Go
/
Triagem de Portadores Genéticos
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article