Early onset or syndromic epilepsy

Gene: EEF1A2

PMID: 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

• 32160274

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

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)

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

• 27441201
• 28378778

NHS Genomic Medicine Service consideration - the phenotype is appropriate for this panel

Created: 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

• 23033978, 23647072, 28911200, 28378778, 27652284

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

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)