Mutations in SCN2A have been associated with benign familial neonatal-infantile seizures (BFNIS) as well as infantile-onset epileptic encephalopathy, such as Ohtahara syndrome (OS). We describe a family with 3 affected individuals carrying the novel SCN2A missense variant c.1147C>G, p.Q383E affecting a residue proximal to the highly conserved selectivity filter in the P-loop of the voltage-gated sodium channel (Nav1.2). All 3 individuals presented with seizures in early infancy. However, there were striking differences in the spectrum of clinical presentations, ranging from BFNIS to OS. A change of ion selectivity of Nav1.2 is considered to be the potential pathomechanism underlying this Nav1.2 channel dysfunction. The observation of benign and severe phenotypes due to an identical mutation within one family contradicts the hypothesis of different modes of inheritance as a mandatory feature discriminating BFNIS from SCN2A encephalopathy.
Division of Child Neurology and Inherited Metabolic Diseases, Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Tübingen, Germany; Department of Women and Child Health, Hospital for Children and Adolescents, Tübingen, Germany.
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ont., Canada; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
Department of Women and Child Health, Hospital for Children and Adolescents, Tübingen, Germany.
CeGaT GmbH, Tübingen, Germany.
Department of Imaging and Radiotherapy, Section Pediatric Radiology, University of Leipzig Hospitals and Clinics, Leipzig, Germany.
Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany.
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