Functional Characterization of a De Novo SCN2A Mixed Variant Linked to Early Infantile Developmental and Epileptic Encephalopathy

Neurology Genetics 2026 Open access

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Authors: Anna Corradi, Antonella Riva, Bruno Sterlini, Lisastella Morinelli, Alessandra Ludovico, Francesca Madia, Pasquale Striano, Martina Albini, Paola Vitale, Michael Pusch, Giulia Lombardo, Maurizio Elia
+5 more Nicolas Chatron, Gaëtan Lesca, Federico Zara, Raffaele Falsaperla, Loretta Ferrera
DOI: 10.1212/nxg.0000000000200344
Cited by: 0

Abstract

Pathogenic variants in the SCN2A gene, encoding the α-subunit type 2 of the voltage-gated sodium channel NaV1.2, cause a phenotypic spectrum including 4 major disorders as benign familial infantile seizures, developmental and epileptic encephalopathy, intellectual disability, and autism. Gain-of-function variants resulting phenotypes may be treated with sodium channel blockers, while loss-of-function (LoF) conditions are non-respondent. We focused on the effects of the pathogenic SCN2A variant c.4976C>T (p.A1659V) found in heterozygosity in 3 patients affected by DEE non responsive to SCB. We functionally investigated this previously uncharacterized SCN2A variant.

Fields of Study & Subjects

Epilepsy research and treatment Ion channel regulation and function Genomics and Rare Diseases

Publication details

Journal / source
Neurology Genetics
Volume
12
Issue
1
Pages
e200344–e200344
Publication date
1 February 2026
Language
EN