title: De novo SCN8A mutation identified by whole-exome sequencing in a boy with neonatal epileptic encephalopathy, multiple congenital anomalies, and movement disorders.
abstract: Epileptic encephalopathies represent a clinically and genetically heterogeneous group of disorders, majority of which are of unknown etiology. We used whole-exome sequencing of a parent-offspring trio to identify the cause of early infantile epileptic encephalopathy in a boy with neonatal seizures, movement disorders, and multiple congenital anomalies who died at the age of 17 months because of respiratory illness and identified a de novo heterozygous missense mutation (c.3979A>G; p.Ile1327Val) in SCN8A (voltage-gated sodium-channel type VIII alpha subunit) gene. The variant was confirmed in the proband with Sanger sequencing. Because the clinical phenotype associated with SCN8A mutations has previously been identified only in a few patients with or without epileptic seizures, these data together with our results suggest that mutations in SCN8A can lead to early infantile epileptic encephalopathy with a broad phenotypic spectrum. Additional investigations will be worthwhile to determine the prevalence and contribution of SCN8A mutations to epileptic encephalopathies.
authors.affiliation: Children's Clinic, Tartu University Hospital, Tartu, Estonia ulvi.vaher@kliinikum.ee.
authors.forename: Ulvi
authors.initials: U
authors.lastname: Vaher
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Margit
authors.initials: M
authors.lastname: Nõukas
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Tiit
authors.initials: T
authors.lastname: Nikopensius
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Mart
authors.initials: M
authors.lastname: Kals
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Tarmo
authors.initials: T
authors.lastname: Annilo
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Mari
authors.initials: M
authors.lastname: Nelis
authors.affiliation: Children's Clinic, Tartu University Hospital, Tartu, Estonia Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
authors.forename: Katrin
authors.initials: K
authors.lastname: Ounap
authors.affiliation: Children's Clinic, Tartu University Hospital, Tartu, Estonia Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia.
authors.forename: Tiia
authors.initials: T
authors.lastname: Reimand
authors.affiliation: Children's Clinic, Tartu University Hospital, Tartu, Estonia Department of Pediatrics, University of Tartu, Tartu, Estonia.
authors.forename: Inga
authors.initials: I
authors.lastname: Talvik
authors.affiliation: Radiology Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Pilvi
authors.initials: P
authors.lastname: Ilves
authors.affiliation: Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Piirsoo
authors.affiliation: Institute of Biomedicine, Department of Pathophysiology, University of Tartu, Tartu, Estonia.
authors.forename: Enn
authors.initials: E
authors.lastname: Seppet
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: Children's Clinic, Tartu University Hospital, Tartu, Estonia Department of Pediatrics, University of Tartu, Tartu, Estonia.
authors.forename: Tiina
authors.initials: T
authors.lastname: Talvik
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D004827:Epilepsy / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009069:Movement Disorders / Q000150:complications / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; C100681:SCN8A protein, human
keywords: SCN8A; epileptic encephalopathy; exome sequencing