Early onset or syndromic epilepsy

Gene: EMC10

Green List (high evidence)

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

• 32869858
• 33531666

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

Green List (high evidence)

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: Literature

Created: 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

• 32869858
• 33531666