title: Phenotypic Variability from Benign Infantile Epilepsy to Ohtahara Syndrome Associated with a Novel Mutation inSCN2A.
abstract: Mutations inSCN2Ahave 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 novelSCN2Amissense 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 fromSCN2Aencephalopathy.
authors: 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.
authors: Steffen
authors: S
authors: Syrbe
authors: 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.
authors: Boris S
authors: BS
authors: Zhorov
authors: Department of Women and Child Health, Hospital for Children and Adolescents, Tübingen, Germany.
authors: Astrid
authors: A
authors: Bertsche
authors: Department of Women and Child Health, Hospital for Children and Adolescents, Tübingen, Germany.
authors: Matthias K
authors: MK
authors: Bernhard
authors: Department of Women and Child Health, Hospital for Children and Adolescents, Tübingen, Germany.
authors: Frauke
authors: F
authors: Hornemann
authors: 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.
authors: Ulrike
authors: U
authors: Mütze
authors: CeGaT GmbH, Tübingen, Germany.
authors: Jessica
authors: J
authors: Hoffmann
authors: CeGaT GmbH, Tübingen, Germany.
authors: Konstanze
authors: K
authors: Hörtnagel
authors: Department of Women and Child Health, Hospital for Children and Adolescents, Tübingen, Germany.
authors: Wieland
authors: W
authors: Kiess
authors: Department of Imaging and Radiotherapy, Section Pediatric Radiology, University of Leipzig Hospitals and Clinics, Leipzig, Germany.
authors: Franz W
authors: FW
authors: Hirsch
authors: Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany.
authors: Johannes R
authors: JR
authors: Lemke
authors: Department of Women and Child Health, Hospital for Children and Adolescents, Tübingen, Germany.
authors: Andreas
authors: A
authors: Merkenschlager
keywords: Brain atrophy; Channelopathy; Early-onset epileptic encephalopathy; Epilepsy