Early onset or syndromic epilepsy

Gene: GNB1

Comment on mode of pathogenicity: Gen2Phen entry for GNB1 (https://www.ebi.ac.uk/gene2phenotype/gfd?dbID=2121) lists the mutation consequence summary as Activating

Created: 14 Sep 2021, 6 p.m. | Last Modified: 14 Sep 2021, 6 p.m.

Panel Version: 2.421

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. 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)

germline de novo GNB1 mutation that overlaps a set of five recurrent somatic tumor mutations for which recent functional studies demonstrated a gain-of-function effect due to constitutive activation of G protein downstream signaling cascades for some of the affected residues (PMID: 27108799)

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
Mental retardation , 616973

Publications

• 27108799

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments

Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases (more than 20), and external review comment all support gene-disease association.

Created: 16 Nov 2018, 3:33 p.m.

Comment on publications: 13 unrelated patients with autosomal dominant mental retardation-42 Petrovski et al. (2016) PMID:27108799 identified 9 different de novo heterozygous missense mutations in the GNB1 gene, the variants were confirmed by Sanger sequencing.

Created: 16 Nov 2018, 3:31 p.m.

Comment on phenotypes: correction of the MIMid

Created: 16 Nov 2018, 3:20 p.m.

Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel

Created: 16 Nov 2018, 3:16 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this intellectual disability syndrome.

Created: 14 Aug 2018, 11 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Mental retardation, autosomal dominant 42, MIM#616973

Publications

• 27108799

Variants in this GENE are reported as part of current diagnostic practice