Early onset or syndromic epilepsy

Gene: EIF2B1

As a result of watchlist tag audit the watchlist tag was removed from EIF2B1- this is now a green gene with sufficient evidence/review

Created: 13 Jan 2020, 1:34 p.m. | Last Modified: 13 Jan 2020, 1:34 p.m.

Panel Version: 2.0

Green List (high evidence)

Vanishing white matter disorder can be associated with seizures.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukoencephalopathy with vanishing white matter, 603896

Publications

• 25843247
• 25761052

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Epilepsy is a feature of Vanishing White Matter Disorder, and therefore should include on the panel for early diagnosis in children. Promoted from Amber to Green.

Created: 13 Aug 2019, 4:17 p.m. | Last Modified: 15 Aug 2019, 8:05 a.m.

Panel Version: 1.222

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: Alison Callaway and 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

Comment on list classification: Kept rating as Amber after discussion in Genomics England Curation team. Although other EIF2B subunits are also associated with Vanishing white matter (VWM) and rated Green on the panel, there are currently insufficient clinical/literature cases of patients with EIF2B1 and seizures (2 patients in PMIDs 25761052 and 25843247). Therefore added 'watchlist' tag while awaiting further cases.

Created: 3 Dec 2018, 11:50 a.m.

In a 2-year-old Chinese girl (case 29) with MIM:603896, Zhang et al. (2015, PMID:25761052) identified a homozygous c(c.328A-G, NM_001414) in exon 4 of the EIF2B1 gene (KL110E). The patient had seizures.

Created: 26 Nov 2018, 11:46 a.m.

In a 61-year-old Japanese woman (Patient 1), born of consanguineous parents, with leukoencephalopathy with vanishing white matter (MIM:603896), Shimada et al. (2015, PMID:25843247) identified a homozygous c.715T-G transversion in exon 8 of the EIF2B1 gene (p.F239V). Symptoms included seizures.

Created: 26 Nov 2018, 11:46 a.m.

Green List (high evidence)

Seizures are a feature of this leukodystrophy

Created: 13 Aug 2018, 11:32 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukoencephalopathy with vanishing white matter, MIM#603896

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