Early onset or syndromic epilepsy

Gene: NDUFA1

I don't know

Comment on mode of inheritance: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that MOI should be updated from XLR to XLD.

Created: 25 Nov 2019, 9:18 p.m. | Last Modified: 25 Nov 2019, 9:18 p.m.

Panel Version: 1.468

Comment on mode of inheritance: There is a case of female with variant and symptoms in PMID:21596602. (Mayr et al., 2011), but she does not have epilepsy but rather a metabolic defect. Therefore XLD is appropriate for metabolism panel but MOI is kept as XLR on this epilepsy panel for now.

Created: 13 Aug 2019, 1:26 p.m. | Last Modified: 13 Aug 2019, 1:26 p.m.

Panel Version: 1.211

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)

XLR mitochondrial complex 1 defic - nuclear type 12. Fernandez-Moreira et al, 2007 - 2 unrelated Spanish patients - diff hemizyogus mutations identified, one had myoclonic epilepsy the other did not (this one also had an aff borther - IVF treatment diff dads). Potluri et al, 2009 - 2 first cousin males mat related - both had seizures amongst other features - hemizygous missense variant. Mayr et al, 2011 - also found a female het for this female with a very mild form of disease - no epilepsy - skewed X-inactivation reported. Bindu et al, 2018 - patient reported with hem missense variant - had epilepsy.

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

Panel Version: 1.188

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Mitochondrial complex I deficiency, nuclear type 12, 301020

Publications

• 19185523
• 25356405

Comment on list classification: Promoted from amber to green. Both OMIM and Gene2Phenotype confirm that NDUFA1 is associated with Mitochondrial complex I deficiency and seizures is listed on both databases as a phenotype. There are three papers (PMID: 17262856,19185523, 29272804) reporting on 4 individuals with variants in the NDUFA1 gene and have seizures. There are currently 2 different NDUFA1 variants reported that are associated with Mitochondrial complex I deficiency.

Created: 27 Nov 2018, 4:24 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 17 Aug 2018, 9:21 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Mitochondrial complex I deficiency, MIM#252010

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