Early onset or syndromic epilepsy
Gene: NDUFAF2
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
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
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.
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
Source Wessex and West Midlands GLH was added to NDUFAF2.
Source NHS GMS was added to NDUFAF2.
Zornitza Stark: Seizures are part of the pheno
Gene: ndufaf2 has been classified as Green List (High Evidence).
Gene: ndufaf2 has been classified as Green List (High Evidence).
Publications for gene: NDUFAF2 were set to
Mode of inheritance for gene: NDUFAF2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFAF2 were changed from to Mitochondrial complex I deficiency, 252010
Expert Review Amber was added to NDUFAF2. Panel: Genetic Epilepsy Syndromes
NDUFAF2 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
NDUFAF2 was created by Sarah Leigh