Early onset or syndromic epilepsy

Gene: NDUFAF2

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 mitochondrial complex 1 defic - nuclear type 10. Ogilvie et al, 2005 - severe childhood-onset progressive encephalopathy - no seizures/epilepsy reported. Calvo et al,2010 - 2 patients with reported NDUFAF2 variants - neither reported to have seizures/epilepsy. Barghuti et al, 2008 - 2 unrelated patients - patient 1 had multiple myocolonic seizures in hospital after being found apneic and cyanotic. Patient 2 - seizures/epilepsy not reported as a feature. Koene et al, 2012 - boy with a hom deletion of exons 2-4 - developed epilepsy with generalised seizures.

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

Panel Version: 1.188

Phenotypes
Mitochondrial complex I deficiency, nuclear type 10, 618233

Publications

• 18180188

Comment on list classification: Promoted from amber to green. NDUFAF2 is confirmed to be associated with complex I deficiency on OMIM and listed as a probable causative gene on Gene2Phenotype. Both websites list seizures as a phenotype of the disease.
There are reports (PMID: 18180188, 26795593, 22644603) of 3 unrelated patients diagnosed with Leigh syndrome or mitochondrial complex I deficiency with different NDUFAF2 variants who have seizures.

Created: 28 Nov 2018, 1:07 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 17 Aug 2018, 9:35 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