Early onset or syndromic epilepsy
Gene: EEF1A2PMID: 32160274 - Davies et al 2020 - several reports of de novo missense mutations in EEF1A2 associated with neurodevelopmental disorders but no clear loss of function mutations. They created mice with a missense mutation in EEF1A2 (D252H) in both heterozygous and homozygous state and EEF1A2 null mutant mice and analysed using behavioural and motor phenotyping alongside molecular modelling and analysis of binding partners. They found the D252H homozygous mice were more severely affected than null homozygotes on the same genetic background. The results suggest that the D252H mutation results in a gain of function.Created: 30 Jul 2020, 10:27 a.m. | Last Modified: 30 Jul 2020, 10:29 a.m.
Panel Version: 2.129
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
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 MR 38 and AD EIEE 33. AD MR 38 is thought to be a less severe disorder with overlapping features seizures have been reported in 1/2 unrelated cases- Nakajima et al, 2015 - de novo het variants identifed - no funtional work done. AD EIEE 33 - De Ligt et al, 2012 - seizures at 4 months de novo het missense mutation, no functional work done. Veerameh et al, 2013 - seizures developed at 10 weeks - de novo het missense variant (same as prev reported), no functional work done. Not enough evidence to put on panel. Lam et al, 2016 (DDD project) - in this paper they say that 3 mutations have been reported previoulsy in 5 patients (G70S x3 - unrelated cases) and two other variants Glu122Lys and Asp252His - and another two cases with the Glu122Lys were reported in 2015. Here they discuss 7 cases each with a diff mutation - 5 of whixh are newly described and all assoc with epilepsy and ID - all missense and de novo - no functional work done.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, 616409; Mental retardation , 616393
Publications
NHS Genomic Medicine Service consideration - the phenotype is appropriate for this panelCreated: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.
Panel Version: 2.491
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.
Panel Version: 2.491
Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 3 variants reported in unrelated cases, together with supportive animal model (PMID: 28378778).Created: 3 Sep 2018, 1:22 p.m.
Comment on mode of inheritance: Biallelic variants reported in mouse model.Created: 3 Sep 2018, 1:11 p.m.
Both mono allelic and bi-allelic variants in this gene have been reported as causing neurodevelopmental phenotypes, including seizures, plus additional evidence from mouse model.Created: 13 Aug 2018, 11:29 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Epileptic encephalopathy, early infantile, 33, MIM#616409
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of pathogenicity for gene: EEF1A2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Tag for-review was removed from gene: EEF1A2.
Tag for-review tag was added to gene: EEF1A2.
Source Wessex and West Midlands GLH was added to EEF1A2.
Source NHS GMS was added to EEF1A2.
Zornitza Stark: Both mono allelic and bi-allel
Gene: eef1a2 has been classified as Green List (High Evidence).
Gene: eef1a2 has been classified as Green List (High Evidence).
Mode of inheritance for gene: EEF1A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: eef1a2 has been classified as Green List (High Evidence).
Publications for gene: EEF1A2 were set to 23033978; 23647072; 28911200; 28378778; 27652284; 30109124
Phenotypes for gene: EEF1A2 were set to Epileptic encephalopathy, early infantile, 33 616409
Publications for gene: EEF1A2 were set to 23033978, 23647072, 28911200, 28378778, 27652284; 30109124
Mode of inheritance for gene: EEF1A2 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Expert Review Amber was added to EEF1A2. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to EEF1A2. Panel: Genetic Epilepsy Syndromes
EEF1A2 was added to Genetic Epilepsy Syndromes panel. Sources: Radboud University Medical Center, Nijmegen,Expert Review Red
EEF1A2 was created by Sarah Leigh