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Genetic epilepsy syndromes

Gene: EIF2S3

Green List (high evidence)

EIF2S3 (eukaryotic translation initiation factor 2 subunit gamma)
EnsemblGeneIds (GRCh38): ENSG00000130741
EnsemblGeneIds (GRCh37): ENSG00000130741
OMIM: 300161, Gene2Phenotype
EIF2S3 is in 7 panels

3 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

XLR MEHMO syndrome - mentasl retardation, epileptic seizures, hypogonadsm and hypogenitalism, microcephaly and obesity - life expectancy less than 2 years. Moortgat et al, 2016 - 2 teenage mat half brothers, unrelated Belgian parents - 1 developed seizures aged 9 months, the other didn't. A male infant from a second family - Spanish origin - onset of seizures at 10 months and died at 12 months, also 3 other male family members reported to have had a similar phenotype with early death2 diff hemizygous variants identified in these families - 1 missense and 1 fs - more severe pheno with this one. Skopkova et al, 2017 - 3 additional patients with MEHMO - 2 buys from nonconsang Slovakian families (both had epileptic seizures) and a 5 year old boy from nonconsang US family (no seizures) and also the original patient reported by Steinmuller et al, 1998 who had seizures - the same fs seen in 3 families and a missense in the other (milder pheno). 6 families in total 5/6 had 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
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
MEHMO syndrome, 300148

Publications

Rebecca Foulger (Genomics England curator)

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
Comment on list classification: Updated rating from Amber to Green: Probable rating in Gene2Phenotype for 'Syndromic ID with severe microcephaly' but sufficient unrelated cases (>3) of seizures in MEHMO patients from literature (PMIDs 23063529,27333055,28055140).
Created: 29 Nov 2018, 10:43 a.m.
Comment on mode of inheritance: X-linked recessive MOI supported by OMIM and literature.
Created: 29 Nov 2018, 10:41 a.m.
Skopkova et al 2017 (PMID:28055140) identified a C-terminal frameshift mutation (Ile465Serfs) in the EIF2S3 gene in three families with MEHMO syndrome and a novel maternally inherited missense EIF2S3 variant (c.324T>A; p.Ser108Arg) in another male patient with less severe clinical symptoms. Two of the families had members with seizures amongst their phenotypes.
Created: 29 Nov 2018, 10:39 a.m.
Moortgat et al, 2016 (PMID:27333055) examined syndromic intellectual disability in two unrelated families with suspected X-linked inheritance. In both families, affected males presented with severe intellectual disability, microcephaly, growth retardation, and epilepsy in most individuals. A missense variant(c.777T>G p.(Ile259Met)) and a frameshift variant (c.1394_1397del p.(Ile465Serfs*4)) were identified in the EIF2S3 gene in the hemizygous state in affected patients, and in the heterozygous states female obligate carriers.
Created: 29 Nov 2018, 10:39 a.m.
Borck et al., 2012 (PMID:23063529) ascertained a family of Morocco Jewish ancestry in which three male individuals were affected by X-linked intellectual disability (ID). Individual III:2 had generalized seizures.
Created: 29 Nov 2018, 10:38 a.m.
Steinmuller et al 1998 (PMID:9781023) describe MEHMO syndrome with clinical hallmarks of mental retardation, epileptic seizures, hypogonadism, and -genitalism, microcephaly and obesity. They studied one large family with X-linked recessive inheritance (5 males affected, including 3 deceased and 1 terminated pregnancy). They don't identify the gene itself, but link the disease to a region of the X-chromosome.
Created: 29 Nov 2018, 10:30 a.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Seizures are a feature of this intellectual disability syndrome.
Created: 13 Aug 2018, 11:41 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
MEHMO syndrome, MIM#300148

Publications

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

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • MEHMO syndrome, 300148
OMIM
300161
Clinvar variants
Variants in EIF2S3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to EIF2S3.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to EIF2S3.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: Seizures are a feature of this

29 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: eif2s3 has been classified as Green List (High Evidence).

29 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: eif2s3 has been classified as Green List (High Evidence).

29 Nov 2018, Gel status: 2

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: EIF2S3 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females

29 Nov 2018, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: EIF2S3 were set to

29 Nov 2018, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: EIF2S3 were changed from to MEHMO syndrome, 300148

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to EIF2S3. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

EIF2S3 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

EIF2S3 was created by Sarah Leigh