Early onset or syndromic epilepsy

Gene: TRA2B

This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:36549593 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tag

Created: 16 Oct 2023, 7:41 p.m. | Last Modified: 16 Oct 2023, 7:41 p.m.

Panel Version: 4.118

Green List (high evidence)

Comment on phenotypes: OMIM phenotype accessed on 20-03-2026

Created: 20 Mar 2026, 11:32 a.m. | Last Modified: 20 Mar 2026, 11:32 a.m.

Panel Version: 8.162

The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, noon | Last Modified: 11 Oct 2023, noon

Panel Version: 4.110

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There is sufficient evidence (7 unrelated cases) for rating this gene as GREEN in the next GMS review.

Created: 1 Jun 2023, 3:04 p.m. | Last Modified: 1 Jun 2023, 3:04 p.m.

Panel Version: 4.46

PMID:36549593 reported 12 individuals from 11 unrelated families identified with 11 different heterozygous variants in TRA2B gene. The variants arose de novo in 10 families, while the variant was inherited from father to son in one family. 6 variants were expected to disrupt the translation start site in exon 1 (start-loss variants), 3 were expected to disrupt the splicing process at the exon 2/3 boundary (splice-affecting variants), and the remaining 2 were expected to produce a premature stop codon (truncating variants).

These patients presented with a neurodevelopmental disorder comprising developmental delay/ intellectual disability (in all patients), axial or global hypotonia (10 patients), delayed motor milestones (all patients), behavioural issues (8 patients), speech impairment (9 patients), epilepsy (7 patients, initial presentation as infantile spasms in 6 and unclassified epileptic encephalopathy in 1), brain abnormalities (10 patients) and microcephaly (5 patients).

In addition, functional studies in mice showed that heterozygous knockout mice developed normal, while complete knockout mice cannot develop embryonically.

This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature

Created: 1 Jun 2023, 2:47 p.m. | Last Modified: 1 Jun 2023, 3:01 p.m.

Panel Version: 4.45

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027

Publications

• 36549593