GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy. (9th December 2015)

• Record Type: Journal Article
• Authors: Papandreou, Apostolos; McTague, Amy; Trump, Natalie; Ambegaonkar, Gautam; Ngoh, Adeline; Meyer, Esther; Scott, Richard H; Kurian, Manju A
• Is Part Of: Developmental medicine & child neurology. Volume 58:Number 4(2016:Apr.)
• Page Start: 416
• Page End: 420
• Publication Date: 2015-12-09
• Subjects: Child development -- Periodicals; Pediatric neurology -- Periodicals; 616.8
• DOI: 10.1111/dmcn.12976
• Languages: English
• ISSNs: 0012-1622

Abstract

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. Abstract : This article is commented on by Pearl on pages330–331 of this issue.