Early onset or syndromic epilepsy

Gene: ASNS

Green List (high evidence)

Seizures appear to be associated with disease in a number of cases:

Ruzzo et al 2013 - 9 patients from 4 unrelated families with a similar phenotype - patients in 3 families developed early-onset seizures. 3 diff hom/compound het missense mutations in the ASNS gene.

Sun et al 2017 - 2 sisters from a consanguineous Indian family. Neither had epilepsy but one had an hyperekplexia and other had an abnormal EEG - one died at 6 months and the other at 11 days. Identified a hom missense variant.

Abhyankar et al 2018 - infant - presented at birth with seizures and other features. Compound het ASNS gene variants.

Gupta et al 2017 - onset of generalised tonic-clonic and multifocal seizures at 3 months of age along with other features. Hom missense variant identified in the ASNS gene.

Sacharow et al 2018 - brother and sister in whom seizures began in both sibs around 6 months of age. Other features noted. Hom missense variant identified in the ASNS gene.

Created: 27 Apr 2022, 8:56 a.m. | Last Modified: 27 Apr 2022, 8:56 a.m.

Panel Version: 2.518

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Asparagine Synthetase deficiency

Publications

• 24139043
• 27469131
• 29375865
• 28776279
• 29279279

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.

Panel Version: 2.491

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 25 Jan 2021, 4:56 p.m. | Last Modified: 25 Jan 2021, 4:56 p.m.

Panel Version: 2.270

Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least four variants reported in at least five unrelated cases with seizures.

Created: 25 Jan 2021, 4:56 p.m. | Last Modified: 25 Jan 2021, 4:56 p.m.

Panel Version: 2.269

Green List (high evidence)

Encephalopathy, including seizures is a feature of this metabolic condition.
Sources: Expert list

Created: 7 Jan 2020, 7:53 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Asparagine synthetase deficiency, MIM# 615574