Pathogenic variants in SCN2A are associated with various neurological disorders including epilepsy, autism spectrum disorder and intellectual disability.
Our study on the functional consequences of SCN2A variants causing the distinct phenotypes of EE, BFNIE and ID contributes to the elucidation of mechanisms underlying the broad phenotypic variability reported for SCN2A variants.
We report that mice heterozygous for the gene Scn2a, a site of frequent de novo mutations in humans with intellectual disability, displayed impaired spatial memory.
The sodium channel, voltage-gated type II α subunit gene SCN2A has been shown to exhibit loss-of-function (LoF) mutations in individuals with seizure disorders, ID, autism and schizophrenia.
Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding.
Mutations in KCNQ2 and SCN2A also contribute to severe infantile epileptic encephalopathies (IEEs) in which seizures and intellectual disability co-occur.
Recently, microduplication of chromosome 2q24.3 (containing eight genes including SCN2A, SCN3A, and the 3' end of SCN1A) was reported in a family with dominantly inherited neonatal seizures and intellectual disability.
Using a clinical exon-targeted oligonucleotide array comparative genomic hybridization (aCGH), we have identified a de novo ~110-kb deletion involving exons 1-2 of SCN2A and non-coding exon 1a of SCN3A in a 25-year-old female with mental retardation, neurobehavioral and psychiatric abnormalities, and a history of infantile seizures with abnormal EEG.
A family with dominantly inherited neonatal seizures and intellectual disability was atypical for neonatal and infantile seizure syndromes associated with potassium (KCNQ2 and KCNQ3) and sodium (SCN2A) channel mutations.