Early onset or syndromic epilepsy

Gene: NGLY1

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

AR congenital disorder of glycosylation type 1A. Need et al, 2012 and Shashi, 2013 - boy with a CDG phenotype incl intractable mutlifocal epilepsy - compound het for a fs and a nonsense variant - looked a tprotein expression in blood leukocytes. Enns et al, 2014 - 8 patients from 5 families with CCDG - all patients had EEG abnormalities and 4 patients (from 4 diff families) developed seizures usually intractable - hom stop mutation in 5 patients from 3 families - all caucasian, European ethnicity - ? founder effect. Other two patients had bialleleic mutations.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Comment on list classification: Promoted to Green due to expert review and enough evidence for N-glycanase 1 deficiency to cause seizures.

Created: 11 Dec 2018, 9:30 a.m.

Comment on list classification: Promoted to Green due to expert review and enough evidence for N-glycanase 1 deficiency to cause seizures.

Created: 11 Dec 2018, 9:29 a.m.

Comment on publications: PMID: 24651605 - 4 out of 8 patients with deficiency of N-glycanase 1 had seizures as a clinical feature.

Created: 11 Dec 2018, 9:28 a.m.

Comment on publications: PMID: 22581936 - describes a male proband with developmental delay, multifocal epilepsy, involuntary movements, abnormal liver function, absent tears. Sequencing revealed a frameshift variant inherited from his mother and a nonsense mutation from his father.

Created: 11 Dec 2018, 9:23 a.m.

Comment on list classification: This is a Green gene on the Congenital disorders of glycosylation (Version 1.20) gene panel, with more than 4 families/cases with Congenital disorder of deglycosylation reported with variants in this gene.

Created: 11 Dec 2018, 9:13 a.m.

Green List (high evidence)

Seizures are part of the phenotype.

Created: 17 Aug 2018, 10:55 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of deglycosylation, MIM#615273

Publications

• 24651605

Variants in this GENE are reported as part of current diagnostic practice