Early onset or syndromic epilepsy

Gene: NDUFAF3

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 is a case report of a compound heterozygote child with myoclonic seizures and complex I deficiency, PMID 19463891.

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 18, 618240

Publications

• 19463981

Comment on list classification: There are 3 cases supporting the association of NDUFAF3 with Mitochondrial complex I deficiency, but only two cases with seizures to date so keeping this gene Amber until further cases verify the association with seizures.

Created: 5 Dec 2018, 8:30 p.m.

Associated with Mitochondrial complex I deficiency in OMIM but not Gene2Phenotype.

PMID: 19463981 (Saada et al. 2009) report 5 patients from 3 families with severe mitochondrial complex I deficiency and lactic acidosis with homozygous or compound heterozygous mutations in the NDUFAF3 gene (3 variants). All patients died before age 6 months. Seizures were observed in 2 individuals from unrelated families. Functional studies show that NDUFAF3 is required for complex I assembly, but the effect of specific mutations was not examined.

Created: 5 Dec 2018, 8:27 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 17 Aug 2018, 9:38 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