Early onset or syndromic epilepsy

Gene: NDUFS1

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: Alison Callaway and John Taylor. Suggested gene rating: Amber.

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

Panel Version: 1.189

I don't know

better tested through the mito panel. Mitochondrial disorders can associated with seizures, but the evidence is not specifically implicated. There are several reports of disease-causing variants being associated with complex I deficiency.

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
Mitochondrial complex I deficiency, nuclear type 5, 618226

Publications

• 11349233

Comment on list classification: Keeping this gene amber on this panel, because although there are enough cases to associate the gene with the disease possible epilepsy/seizures have only been observed in 2 cases.

Created: 6 Dec 2018, 11:47 a.m.

Associated with Mitochondrial complex I deficiency in OMIM and LEIGH SYNDROME and MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY in Gene2Phenotype.

PMID: 11349233 (Benit et al. 2001) - In 3 of 36 patients with isolated mitochondrial complex I deficiency (252010), Benit et al. (2001) identified 5 different point mutations and 1 large-scale deletion in the NDUFS1 gene. None of these patients presented with seizures.

PMID: 20382551 (Hoefs et al. 2010) - report homozygous or compound heterozygous variants in NDUFS1 gene in 3 families. Seizures were only observed in 1 patient (episodic brainstem events)

PMID: 25615419 (Björkman et al 2015) - 3 patients from 2 families with homozygous or compound heterozygous mutations in NDUFS1. 1 patient had frequent apneas that were treated with phenobarbital because of suspected epileptic origin

Created: 6 Dec 2018, 11:45 a.m.

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 17 Aug 2018, 9:57 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, MIM#252010

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