White matter disorders and cerebral calcification - narrow panel
Gene: EPRS
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.
Panel Version: 2.9
Comment on list classification: promoting from grey to amber but with recommendation for green rating following GMS review. 4 unrelated cases, presentation before age of 18.Created: 28 Apr 2021, 4:31 p.m. | Last Modified: 28 Apr 2021, 4:31 p.m.
Panel Version: 1.51
As reported by the expert reviewer PMID: 29576217 (Mendes et al 2018) reports 4 unrelated affected individuals with hypomyelination and biallelic (homozygous or compound het) pathogenic variants in EPRS. 5 variants in total identified (1 nonsense, 1 frameshift, 3 missense). Variants segregated with the disease in all 4 families. All 4 presented initially before the age of 18 and in all brain MRI showed a hypomyelinating leukodystrophy with thinning of the corpus callosum. In 3 cases the variant was identified by WES, in one by direct sequencing of EPRS1.
PMID: 33805425 - Sawaguchi et al 2021 - using a mouse model they show that EPRS1 variant Arg339-to-Ter (R339X) (found in one of the patients in Mendes et al in heterozgyous state with another variant) localizes EPRS1 proteins as polymeric aggregates into Rab7-positive vesicle structures in mouse oligodendroglial FBD-102b cells. Wild-type proteins are distributed throughout the cell bodies. This seems to inhibit cell morphological differentiation.Created: 28 Apr 2021, 4:05 p.m. | Last Modified: 28 Apr 2021, 4:05 p.m.
Panel Version: 1.50
Added new gene name tag - current gene name in HGNC is EPRS1Created: 28 Apr 2021, 3:24 p.m. | Last Modified: 28 Apr 2021, 3:24 p.m.
Panel Version: 1.50
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Leukodystrophy, hypomyelinating, 15, OMIM:617951
Publications
Four unrelated families reported with this neurodegenerative disorder. Onset of motor and cognitive impairment in the first or second decade of life. Features include dystonia, ataxia, spasticity, dysphagia, severe optic atrophy, and some have hearing loss. Brain imaging shows hypomyelinating leukodystrophy with thin corpus callosum.
Sources: Expert listCreated: 15 Sep 2020, 10:12 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Leukodystrophy, hypomyelinating, 15, MIM# 617951
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_21_rating was removed from gene: EPRS.
Source NHS GMS was added to EPRS. Source Expert Review Green was added to EPRS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: EPRS were set to 29576217
Gene: eprs has been classified as Amber List (Moderate Evidence).
Tag Q2_21_rating tag was added to gene: EPRS.
Gene: eprs has been classified as Amber List (Moderate Evidence).
Tag new-gene-name tag was added to gene: EPRS.
gene: EPRS was added gene: EPRS was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list Mode of inheritance for gene: EPRS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EPRS were set to 29576217 Phenotypes for gene: EPRS were set to Leukodystrophy, hypomyelinating, 15, MIM# 617951 Review for gene: EPRS was set to GREEN gene: EPRS was marked as current diagnostic