Variable Clinical Appearance of the Kir2.1 Rare Variants in Russian Patients with Long QT Syndrome.
Genes (Basel)
; 13(4)2022 03 22.
Article
em En
| MEDLINE
| ID: mdl-35456365
ABSTRACT
BACKGROUND:
The KCNJ2 gene encodes inward rectifier Kir2.1 channels, maintaining resting potential and cell excitability. Presumably, clinical phenotypes of mutation carriers correlate with ion permeability defects. Loss-of-function mutations lead to QTc prolongation with variable dysmorphic features, whereas gain-of-function mutations cause short QT syndrome and/or atrial fibrillation.METHODS:
We screened 210 probands with Long QT syndrome for mutations in the KCNJ2 gene. The electrophysiological study was performed for the p.Val93Ile variant in the transfected CHO-K1 cells.RESULTS:
We found three rare genetic variants, p.Arg67Trp, p.Val93Ile, and p.R218Q, in three unrelated LQTS probands. Probands with p.Arg67Trp and p.R218Q had a phenotype typical for Andersen-Tawil (ATS), and the p.Val93Ile carrier had lone QTc prolongation. Variant p.Val93Ile was initially described as a gain-of-function pathogenic mutation causing familial atrial fibrillation. We validated electrophysiological features of this variant in CHO-K1 cells, but no family members of these patients had atrial fibrillation. Using ACMG (2015) criteria, we re-assessed this variant as a variant of unknown significance (class III).CONCLUSIONS:
LQT7 is a rare form of LQTS in Russia, and accounts for 1% of the LQTS cohort. Variant p.Val93Ile leads to a gain-of-function effect in the different cell lines, but its clinical appearance is not so consistent. The clinical significance of this variant might be overestimated.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
/
Síndrome do QT Longo
/
Síndrome de Andersen
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Genes (Basel)
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Federação Russa