Early onset or syndromic epilepsy
Gene: GABRB2
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
AD infantile or early childhood epileptic encephalopahy 2 (IECEE2) - seizure type and severity may vary and may be intractable. Srivastava et al 2014 - 12 year old Spanish girl - developed febrile seizures at 9 months - eventualy developed non-febrile tonic-clonic and subtle seizures - de novo het missense variant. Ishii et al, 2017 - 2 year old boy with generalised tonic-clonic seizures - de novo het missense variant - in vitro functionsal studies done. Hamdan et al, 2017 - 10 unrelated patients - all but 1 had seizures - onset occured between 6 months and 6 years - all types. De novo het missense variants in all.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, infantile or early childhood, 617829
Publications
Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease associationCreated: 22 Nov 2018, 10:47 a.m.
Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green. Hamdan et al. (2017) PMID 29100083 reported 3 unrelated cases with de novo missense variants in GABRB2 who had developmental and epileptic encephalopathy. Srivastava et al. (2014) PMID 25124326 . Ishii et al. (2017) PMID: 27789573 describes a 12-year old girl with intellectual disability and epilepsy due to another de novo missense variant in GABRB2 epileptic seizures. Ishii et al. (2017) PMID 27789573 describes a patient with early myoclonic encephalopathy and severe psycomotor delay, due to a de novo heterozygous missense mutation in GABRB2.Created: 22 Nov 2018, 10:44 a.m.
Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panelCreated: 22 Nov 2018, 10:15 a.m.
Multiple patients from unrelated families reported with de novo variants in this EE gene.Created: 14 Aug 2018, 12:20 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epileptic encephalopathy, infantile or early childhood, 2, MIM#617829
Publications
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to GABRB2.
Source NHS GMS was added to GABRB2.
Zornitza Stark: Multiple patients from unrelat
Gene: gabrb2 has been classified as Green List (High Evidence).
Gene: gabrb2 has been classified as Green List (High Evidence).
Gene: gabrb2 has been classified as Green List (High Evidence).
Mode of inheritance for gene: GABRB2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB2 were set to
Phenotypes for gene: GABRB2 were changed from to Epileptic encephalopathy, infantile or early childhood, 2, 617829
Expert Review Amber was added to GABRB2. Panel: Genetic Epilepsy Syndromes
GABRB2 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
GABRB2 was created by Sarah Leigh