KCNH2 p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort.

Autor: Lorca R; Unidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Junco-Vicente A; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., Pérez-Pérez A; Pediatric Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., Pascual I; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Persia-Paulino YR; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., González-Urbistondo F; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., Cuesta-Llavona E; Unidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Fernández-Barrio BC; Pediatric Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., Morís C; Unidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Rubín JM; Unidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Coto E; Unidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Gómez J; Unidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain.; CIBER-Enfermedades Respiratorias, 28029 Madrid, Spain., Reguero JJR; Unidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain.
Jazyk: angličtina
Zdroj: Life (Basel, Switzerland) [Life (Basel)] 2022 Apr 08; Vol. 12 (4). Date of Electronic Publication: 2022 Apr 08.
DOI: 10.3390/life12040556
Abstrakt: Long QT syndrome (LQTS) is an inherited (autosomal dominant) channelopathy associated with susceptibility to ventricular arrhythmias due to malfunction of ion channels in cardiomyocytes, that could lead to sudden death (SD). Most pathogenic variants are in the main 3 genes: KCNQ1 (LQT1) , KCNH2 (LQT2) and SCN5A (LQT3) . Efforts to improve the understanding of the genotype-phenotype relationship are essential to improve the medical clinical practice. In this study, we identified all index patients referred for NGS genetic sequencing due to LQTS, in a Spanish cohort, who were carriers of a new pathogenic variant ( KCNH2 p.Gly262AlafsTer98). Genetic and clinical family screening was performed in order to describe its phenotypic characteristics. We identified 22 relatives of Romani ethnicity, who were carriers of the variant. Penetrance reached a 100% and adherence to medical treatment was low. There was a high rate of clinical events, particularly arrhythmic events and SD (1 in every 4 patients presented syncope, 1 presented an aborted SD, 2 obligated carriers suffered SD before the age of 40 and 4 out of 6 carriers of an implantable cardioverter-defibrillator (ICD) had appropriate ICD therapies. Correct adherence to medical treatment in all carriers should be specially encouraged in this population. ICD implantation decision in non-compliant patients, and refusing left cardiac sympathetic denervation, should be carefully outweighed.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje