Early onset or syndromic epilepsy

Gene: NARS2

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 combined oxidative phosphorylation deficiency 24 - wide phenotypic variability. Vanlander et al, 2015 - 2 sibs if consang parents - one had epilepsy - hom splice variant. Sofou et al, 2015 - Swedish boy - developed generalised seizures aged 7 months - hom missense variant. Seaver et al, 2018 - two brothers with lethal epileptic encephalopathy - compound het for NARS2 variants. Mizguchi et al, 2017 - 3 unrelated families with infantile onset dev delay/regression and epilepsy - 2 were compund het and 1 hom. Simon et al, 2015 - 2 families - family 1 - unrelated healthy caucasian parents - proband developed complex partial seizures as did an aff brother- compound het for missense and nonsense variants. Family 2 - Pakistani family - no seizures.

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

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency, 616239

Publications

• 25385316
• 25807530
• 30327238

Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association.

Created: 4 Dec 2018, 6:11 p.m.

Comment on publications: Added publications to support upgrading of the gene to Green

Created: 4 Dec 2018, 6:10 p.m.

Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel

Created: 4 Dec 2018, 5:03 p.m.

Comment on mode of inheritance: added MOI from review

Created: 1 Oct 2018, 4:57 p.m.

Comment on mode of inheritance: changed MOI from external reviewer comment

Created: 1 Oct 2018, 4:34 p.m.

Green List (high evidence)

Seizures are reported in some patients with this mitochondrial disorder.

Created: 17 Aug 2018, 8:23 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 24, MIM#616239

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