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Updated: Feb 10, 2026

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
De novo gain-of-function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy
Paolo Ambrosino1, Maria Virginia Soldovieri1, Thomas Bast2,3
1Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, Campobasso, Italy.
Abstract:
Variants in several potassium channel genes have been found in developmental and epileptic encephalopathies (DEE). We report on 2 females with de novo variants in KCNT2 with West syndrome followed by Lennox-Gastaut syndrome or with DEE with migrating focal seizures. After in vitro analysis suggested quinidine-responsive gain-of-function effects, we treated 1 of the girls with quinidine add-on therapy and achieved marked clinical improvements. This suggests that the new spectrum of KCNT2-related disorders do not only share similar phenotypic and in vitro functional and pharmacological features with previously known KCNT1-related disorders, but also represents a further example for possible precision medicine approaches. Ann Neurol 2018;83:1198-1204.
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