Early onset or syndromic epilepsy
Gene: NDUFAF3
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
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
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.
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
Source Wessex and West Midlands GLH was added to NDUFAF3.
Source NHS GMS was added to NDUFAF3.
Zornitza Stark: Seizures are part of the pheno
Gene: ndufaf3 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: NDUFAF3 were changed from to Mitochondrial complex I deficiency 252010
Publications for gene: NDUFAF3 were set to
Mode of inheritance for gene: NDUFAF3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Gene: ndufaf3 has been classified as Amber List (Moderate Evidence).
Expert Review Amber was added to NDUFAF3. Panel: Genetic Epilepsy Syndromes
NDUFAF3 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
NDUFAF3 was created by Sarah Leigh