A novel homozygous KCNQ3 loss-of-function variant causes non-syndromic intellectual disability and neonatal-onset pharmacodependent epilepsy.

Fiche publication


Date publication

septembre 2019

Journal

Epilepsia open

Auteurs

Membres identifiés du Cancéropôle Est :
Pr PHILIPPE Christophe


Tous les auteurs :
Lauritano A, Moutton S, Longobardi E, Tran Mau-Them F, Laudati G, Nappi P, Soldovieri MV, Ambrosino P, Cataldi M, Jouan T, Lehalle D, Maurey H, Philippe C, Miceli F, Vitobello A, Taglialatela M

Résumé

Heterozygous variants in or, more rarely, genes are responsible for early-onset developmental/epileptic disorders characterized by heterogeneous clinical presentation and course, genetic transmission, and prognosis. While familial forms mostly include benign epilepsies with seizures starting in the neonatal or early-infantile period, de novo variants in or have been described in sporadic cases of early-onset encephalopathy (EOEE) with pharmacoresistant seizures, various age-related pathological EEG patterns, and moderate/severe developmental impairment. All pathogenic variants in or occur in heterozygosity. The aim of this work was to report the clinical, molecular, and functional properties of a new variant found in homozygous configuration in a 9-year-old girl with pharmacodependent neonatal-onset epilepsy and non-syndromic intellectual disability.

Mots clés

KCNQ3, early‐onset epileptic encephalopathy, homozygous loss‐of‐function variant, intellectual disability, next‐generation sequencing, nonsense‐mediated mRNA decay

Référence

Epilepsia Open. 2019 Sep;4(3):464-475