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Dev Med Child Neurol. 2016 Apr;58(4):416-20. doi: 10.1111/dmcn.12976. Epub 2015 Dec 9.

GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy.

Author information

1
Genetics and Genomics Medicine Unit, UCL Institute of Child Health, London, UK.
2
Department of Neurology, Great Ormond Street Hospital, London, UK.
3
Developmental Neurosciences Programme, UCL Institute of Child Health, London, UK.
4
Department of Clinical Genetics, Great Ormond Street Hospital, London, UK.
5
Department of Paediatric Neurology, Addenbrooke's Hospital, Cambridge, UK.

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.

PMID:
26645412
PMCID:
PMC4864756
DOI:
10.1111/dmcn.12976
[Indexed for MEDLINE]
Free PMC Article

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