Early onset or syndromic epilepsy

Gene: GABBR2

Comment on publications: PMID: 39028675 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI

Created: 20 Feb 2025, 3:43 p.m. | Last Modified: 20 Feb 2025, 3:43 p.m.

Panel Version: 7.37

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

Missense variants reported, not LOF variants - recurrent de novo variant known (Ala567Thr). AD Early infantile epileptic encepalopathy. 3 unrelated cases - de novo heterozygous missense mutations identified in all. In vitro studies on 2 of these undertaken.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epileptic encephalopathy, early infantile, 59,617904; Neurodevelopmental disorder with poor language and loss of hand skills,617903; {Nicotine dependence, protection against},188890; {Nicotine dependence, susceptibility to},188890

Publications

• 28856709
• 29100083

Red List (low evidence)

Publications

• EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11

Red List (low evidence)

Publications

• EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11

Red List (low evidence)

Publications

• EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11

Red List (low evidence)

Publications

• EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11

Comment on list classification: Confirmed with Richard Scott (Genomics England Clinical Team) that this gene should be promoted to green.

Created: 11 Dec 2017, 9:56 a.m.

Comment on list classification: This is a Possible DD gene for Epileptic encephalopathy. No relevant diseases in OMIM. PMID: 29100083 - 1 patient with a de novo missense variant in this gene in the CENet Cohort is reported. He presented with severe global developmental delay and seizures, with profound intellectual deficiency. PMID: 28061363 - 2 individuals reported with de novo variants in this gene in an analysis by EuroEPINOMICS and Epi4K/EPGP of a large cohort of trios with epileptic encephalopathies, infantile spasms or Lennox Gastaut syndrome. Knock out mice experience spontaneous seizures and severe memory impairment. PMID: 26740508 - de novo missense variant in this gene and a homozygous variant in EIF4G1 were identified in this gene in a female patient with Rett syndrome including severe ID (without seizures). DDD project identified a de novo missense variants in 2 males and a female which were validated (PMID:28135719). PMID: 28856709 - the same de novo variant was identified in four unrelated patients with a Rett-like phenotype.

Created: 8 Dec 2017, 5:15 p.m.

Gene added in expert review of the panel by Richard Scott (Genomics England), Manju Kurian (UCL-Institute of Child Health), Natalie Trump (NHS - Great Ormond Street Hospital), Amy McTague (UCL Institute of Child Health).

Created: 12 Nov 2015, 4:02 p.m.