Early onset or syndromic epilepsy
Gene: EMC10
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 9:39 a.m. | Last Modified: 1 Feb 2023, 9:39 a.m.
Panel Version: 3.29
Comment on list classification: There is now enough evidence to warrant a Green rating at the next GMS panel update.Created: 11 Jun 2021, 10:52 a.m. | Last Modified: 11 Jun 2021, 10:52 a.m.
Panel Version: 3.1124
There are now at least 15 individuals from 8 families reported with biallelic variants in the EMC10 gene associated with disease. One variant found in a single population is likely to be a founder variant; however, the identification of a different variant in a family presenting with a similar phenotype corroborates causality. Both variants were shown to significantly reduce EMC10 RNA expression. All affected individuals show a core phenotype of GDD/ID with variable severity. Seizures were noted in 7/15 individuals, typically during childhood or in the neonatal period, and included multifocal as well as generalized tonic–clonic seizures.Created: 11 Jun 2021, 10:50 a.m. | Last Modified: 11 Jun 2021, 10:50 a.m.
Panel Version: 3.1123
Comment on phenotypes: EMC10 is now associated with a relevant phenotype in OMIM - 'Neurodevelopmental disorder with dysmorphic facies and variable seizures, OMIM:619264' and is listed in G2P with a 'probable' disease confidence rating for 'EMC10-related neurodevelopmental disorder'Created: 11 Jun 2021, 10:21 a.m. | Last Modified: 11 Jun 2021, 10:21 a.m.
Panel Version: 3.1122
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder with dysmorphic facies and variable seizures, OMIM:619264
Publications
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with any phenotypes in OMIM or Gene2Phenotype. As there is only 1 case, this gene has been given a Red rating.Created: 16 Dec 2020, 4:38 p.m. | Last Modified: 16 Dec 2020, 4:38 p.m.
Panel Version: 3.652
PMID 33531666: Additional 12 individuals from 7 Middle Eastern families reported. Same variant in all, suggestive of founder effect (but different to the previously reported family).Created: 10 May 2021, 8:18 a.m. | Last Modified: 10 May 2021, 8:18 a.m.
Panel Version: 3.1069
Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders.
One Saudi family with 2 affected individuals with mild ID, speech delay, and GDD.
WES and Sanger sequencing revealed a homozygous splice acceptor site variant (c.679‐1G>A) in EMC10 . Variant segregated within the family. RT‐qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients.
Sources: LiteratureCreated: 9 Dec 2020, 8:35 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder with dysmorphic facies and variable seizures, MIM# 619264
Publications
Tag Q2_21_rating was removed from gene: EMC10.
Source Expert Review Green was added to EMC10. Source NHS GMS was added to EMC10. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: EMC10 was added gene: EMC10 was added to Genetic epilepsy syndromes. Sources: Expert Review Amber,Literature Q2_21_rating tags were added to gene: EMC10. Mode of inheritance for gene: EMC10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EMC10 were set to 32869858; 33531666 Phenotypes for gene: EMC10 were set to Neurodevelopmental disorder with dysmorphic facies and variable seizures, OMIM:619264