Early onset or syndromic epilepsy

Gene: NDUFA10

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 22. Hoefs et al, 2011 - convulsions - compound het - western blotting and immunoblotting done. Kohda et al, 2016 - Leighs disease - no mention of seizures/epilepsy in supp data - compound het for a missense and a fs, Western blotting done. Minoia et al, 2017 - Italian boy with consang parents with Leigh syndrome. No mention of epilepsy/seizures in him but does have a family history where a pat cousin died at 4 months from an unspecified cardiomyopathy, two mat cousins had an unspecified myopathy and another cousin had EIEE - hom missense variant in boy, both parents carriers. Not sure if other possibly affected family members have had any genetic testing so is the EIEE unrelated?

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 22, 618243

Publications

• 21150889
• 30423443

Comment on list classification: Promoted from amber to green. Both OMIM and Gene2Phenotype have confirmed that NDUFA10 is associated with Leigh syndrome, and both have listed seizures as a phenotype.
There are 3 studies (PMID: 21150889; 26741492; 28247337) reporting 3 patients who have different variants in the NDUFA10 gene and have seizures.

Created: 27 Nov 2018, 5 p.m.

Comment on list classification: Promoted from amber to green. Both OMIM and Gene2Phenotype confirm that NDUFA10 is associated with Leigh syndrome and both databases list seizures as a phenotype.
There are 3 studies (PMID: 21150889, 26741492, 28247337) describing 3 patients who have different variants in NDUFA10 who have seizures.

Created: 27 Nov 2018, 4:59 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 17 Aug 2018, 9:26 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leigh syndrome, MIM#256000

Publications

• 21150889
• 26741492
• 28247337

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