Early onset or syndromic epilepsy

Gene: AJAP1

I don't know

Comment on list classification: Although there are five unrelated cases, the epilepsy phenotype is broad and there is contradictory functional evidence. Hence, this gene is currently rated as amber.

The 'watchlist' tag has been added to keep track of any new evidence.

Created: 11 Nov 2024, 7:03 p.m. | Last Modified: 11 Nov 2024, 7:03 p.m.

Panel Version: 7.7

As reviewed by Hannah Knight, PMID:38985877 reported five unrelated individuals with monoallelic variants or a deletion in AJAP1 gene. Although four of these patients presented with seizures, the type of seizures varied across these individuals.

Two of these five cases had a conclusion of either 'benign' or 'unknown' in their evaluation of pathogenicity, where 'benign' was one of the four cases with seizures, where 'unknown' was the fifth case without seizures. One of the cases (Individual 1) has a missense variant that was evaluated as 'pathogenic'. But, functional studies in monoallelic knock in mice was not clearly supportive of this conclusion and the EEG in this mice appeared equivalent to wild type mouse. In addition, all missense variants of this gene in ClinVar are rated as VUS / benign.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.

Created: 23 Oct 2024, 9:56 a.m. | Last Modified: 11 Nov 2024, 6:49 p.m.

Panel Version: 7.6

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Publications

• 38985877

Green List (high evidence)

PMID: 38985877 (2024) identified five individuals with monoallelic variants or a deletion in AJAP1, who present with epilepsy, neurodevelopmental problems, or intellectual disability
Also included functional work
Sources: Literature

Created: 18 Oct 2024, 11:41 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epileptic seizures; developmental disorder; intellectual disability

Publications

• PMID: 38985877