Early onset or syndromic epilepsy
Gene: GNB1Comment on mode of pathogenicity: Gen2Phen entry for GNB1 (https://www.ebi.ac.uk/gene2phenotype/gfd?dbID=2121) lists the mutation consequence summary as ActivatingCreated: 14 Sep 2021, 6 p.m. | Last Modified: 14 Sep 2021, 6 p.m.
Panel Version: 2.421
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
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
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 MIMidCreated: 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 panelCreated: 16 Nov 2018, 3:16 p.m.
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
Variants in this GENE are reported as part of current diagnostic practice
Mode of pathogenicity for gene: GNB1 was changed from None to Other
Phenotypes for gene: GNB1 were changed from Mental retardation, autosomal dominant 42, 616973; seizures to Mental retardation, autosomal dominant 42 OMIM:616973; intellectual disability, autosomal dominant 42 MONDO:0014855
Source Wessex and West Midlands GLH was added to GNB1.
Source NHS GMS was added to GNB1.
Zornitza Stark: Seizures are part of the pheno
Gene: gnb1 has been classified as Green List (High Evidence).
Gene: gnb1 has been classified as Green List (High Evidence).
Mode of inheritance for gene: GNB1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB1 were set to 27108799; 25529582; 27108799
Publications for gene: GNB1 were set to
Phenotypes for gene: GNB1 were changed from Mental retardation, autosomal dominant 42, 614018; seizures to Mental retardation, autosomal dominant 42, 616973; seizures
Phenotypes for gene: GNB1 were changed from to Mental retardation, autosomal dominant 42, 614018; seizures
Expert Review Amber was added to GNB1. Panel: Genetic Epilepsy Syndromes
GNB1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
GNB1 was created by Sarah Leigh