Your browser doesn't support javascript.
loading
An Interdomain KCNH2 Mutation Produces an Intermediate Long QT Syndrome.
Osterbur, Marika L; Zheng, Renjian; Marion, Robert; Walsh, Christine; McDonald, Thomas V.
Afiliación
  • Osterbur ML; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY.
  • Zheng R; Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY.
  • Marion R; Department of Pediatrics, Division of Genetics, Children's Hospital at Montefiore, Bronx, NY.
  • Walsh C; Department of Pediatrics, Division of Cardiology, Children's Hospital at Montefiore, Bronx, NY.
  • McDonald TV; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY.
Hum Mutat ; 36(8): 764-73, 2015 Aug.
Article en En | MEDLINE | ID: mdl-25914329
Hereditary long QT syndrome is caused by deleterious mutation in one of several genetic loci, including locus LQT2 that contains the KCNH2 gene (or hERG, human ether-a-go-go related gene), causing faulty cardiac repolarization. Here, we describe and characterize a novel mutation, p.Asp219Val in the hERG channel, identified in an 11-year-old male with syncope and prolonged QT interval. Genetic sequencing showed a nonsynonymous variation in KCNH2 (c.656A>T: amino acid p.Asp219Val). p.Asp219Val resides in a region of the channel predicted to be unstructured and flexible, located between the PAS (Per-Arnt-Sim) domain and its interaction sites in the transmembrane domain. The p.Asp219Val hERG channel produced K(+) current that activated with modest changes in voltage dependence. Mutant channels were also slower to inactivate, recovered from inactivation more readily and demonstrated a significantly accelerated deactivation rate compared with the slow deactivation of wild-type channels. The intermediate nature of the biophysical perturbation is consistent with the degree of severity in the clinical phenotype. The findings of this study demonstrate a previously unknown role of the proximal N-terminus in deactivation and support the hypothesis that the proximal N-terminal domain is essential in maintaining slow hERG deactivation.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de QT Prolongado / Canales de Potasio Éter-A-Go-Go / Mutación Tipo de estudio: Prognostic_studies Límite: Child / Humans / Male Idioma: En Revista: Hum Mutat Asunto de la revista: GENETICA MEDICA Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de QT Prolongado / Canales de Potasio Éter-A-Go-Go / Mutación Tipo de estudio: Prognostic_studies Límite: Child / Humans / Male Idioma: En Revista: Hum Mutat Asunto de la revista: GENETICA MEDICA Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos