Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome.

Autor: Lorca R; Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central Asturias, Unidad de Referencia de Cardiopatías Familiares-HUCA, 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., Martin-Fernandez M; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, 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., Aparicio A; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., Barja N; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain., Cuesta-LLavona E; Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central Asturias, Unidad de Referencia de Cardiopatías Familiares-HUCA, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain., Roces L; Anestesiología, Reanimación y terapéutica del dolor, Completo Asistencial Universitario de Salamanca, 37007 Salamanca, Spain., Avanzas P; Heart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain., Moris C; Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central Asturias, Unidad de Referencia de Cardiopatías Familiares-HUCA, 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; Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central Asturias, Unidad de Referencia de Cardiopatías Familiares-HUCA, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain., Rodríguez Reguero JJ; Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central Asturias, Unidad de Referencia de Cardiopatías Familiares-HUCA, 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., Gómez J; Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central Asturias, Unidad de Referencia de Cardiopatías Familiares-HUCA, 33011 Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain.
Jazyk: angličtina
Zdroj: Journal of clinical medicine [J Clin Med] 2020 Nov 26; Vol. 9 (12). Date of Electronic Publication: 2020 Nov 26.
DOI: 10.3390/jcm9123846
Abstrakt: Background: Long QT syndrome (LQTS) is an inheritable arrhythmogenic disorder associated with life-threatening arrhythmic events (LAEs). In general, patients with LQTS2 ( KCNH2 ) and LQTS3 ( SCN5A ) are considered to be a greater risk of LAEs than LQTS1 ( KCNQ1 ) patients. Gender differences are also important. Series analyzing families with the same pathogenic variants may help in the progress of elaborating strong specific genotype-phenotype management strategies. In this manuscript, we describe the phenotype of seven unrelated families, carriers of the KCNQ1 G168R pathogenic variant.
Methods: we identified all consecutive index cases referred for genetic testing with LQTS diagnosis carriers of KCNQ1 G168R variant. Genetic and clinical screening for all available relatives was performed.
Results: we evaluated seven unrelated families, with a total 34 KCNQ1 G168R carriers (two obligated carriers died without available EKGs to evaluate the phenotype). All index cases but one were women and three of them presented with aborted sudden cardiac death (SCD) or syncope. The presence of sudden death in these families is notable, with a total of nine unexplained sudden deaths and four aborted SCD. Phenotype penetrance was 100% in women and 37.5% in men.
Conclusions: KCNQ1 G168R is a pathogenic variant, with a high penetrance among women and mild penetrance among men. Risk for LAEs in this variant seems not negligible, especially among woman, and risk stratification should always be carefully evaluated.
Databáze: MEDLINE
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