title: GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy.
abstract: The gamma-aminobutyric acid type A receptor β3 gene (GABRB3) encodes the β3-subunit of the gamma-aminobutyric acid type A (GABAA ) receptor, which mediates inhibitory signalling within the central nervous system. Recently, GABRB3 mutations have been identified in a few patients with infantile spasms and Lennox-Gastaut syndrome. We report the clinical and electrographic features of a novel case of GABRB3-related early-onset epileptic encephalopathy. Our patient presented with neonatal hypotonia and feeding difficulties, then developed pharmacoresistant epileptic encephalopathy, characterized by multiple seizure types from 3 months of age. Electroencephalography demonstrated ictal generalized and interictal multifocal epileptiform abnormalities. Using a SureSelectXT custom multiple gene panel covering 48 early infantile epileptic encephalopathy/developmental delay genes, a novel de novo GABRB3 heterozygous missense mutation, c.860C>T (p.Thr287Ile), was identified and confirmed on Sanger sequencing. GABRB3 is an emerging cause of early-onset epilepsy. Novel genetic technologies, such as whole-exome/genome sequencing and multiple gene panels, will undoubtedly identify further cases, allowing more detailed electroclinical delineation of the GABRB3-related genotypic and phenotypic spectra.
authors.affiliation: Genetics and Genomics Medicine Unit, UCL Institute of Child Health, London, UK.|Department of Neurology, Great Ormond Street Hospital, London, UK.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papandreou
authors.affiliation: Developmental Neurosciences Programme, UCL Institute of Child Health, London, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: McTague
authors.affiliation: Department of Clinical Genetics, Great Ormond Street Hospital, London, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Trump
authors.affiliation: Department of Paediatric Neurology, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Gautam
authors.initials: G
authors.lastname: Ambegaonkar
authors.affiliation: Developmental Neurosciences Programme, UCL Institute of Child Health, London, UK.
authors.forename: Adeline
authors.initials: A
authors.lastname: Ngoh
authors.affiliation: Department of Neurology, Great Ormond Street Hospital, London, UK.
authors.forename: Esther
authors.initials: E
authors.lastname: Meyer
authors.affiliation: Department of Clinical Genetics, Great Ormond Street Hospital, London, UK.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Scott
authors.affiliation: Department of Neurology, Great Ormond Street Hospital, London, UK.|Developmental Neurosciences Programme, UCL Institute of Child Health, London, UK.
authors.forename: Manju A
authors.initials: MA
authors.lastname: Kurian
mesh_terms: D017668:Age of Onset; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics / Q000503:physiopathology; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011963:Receptors, GABA-A / Q000235:genetics*; D013036:Spasms, Infantile / Q000235:genetics / Q000503:physiopathology
chemical_list: C546273:GABRB3 protein, human; D011963:Receptors, GABA-A