Early onset or syndromic epilepsy

Gene: COQ9

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 primary coenzyme Q10 defic 5. Rahman et al, 2001 - boy - 7th child of healthy unrelated Pakistani parents - presented on day 1 with poor feeding, hypothermia and seizures - muscle biopsy at 10 months showed CoQ10 defic. Fam history showed that 1 sib had died on day 1 with seizures, aminoacdiuria and acidosis and the mother had had 5 first trimester miscarriages - hom stop mutation detected. Danhauser et al, 2016 - male infant born to consang Turkish parents = had seizures amonst other features and died at 18 days old - hom splice site mutation.

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
Coenzyme Q10 deficiency primary, 614654

Publications

• 26081641

Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Coenzyme Q10 deficiency, primary, 5, 614654, although seizures are not mentioned. At least 2 loss of function variants have been reported in two unrelated cases. In vitro studies show that expression of wildtype COQ9 in patient cells carrying homozygous c.521+1del can rescue reduced activity of mitochondrial complex II/III and restore CoQ10 and COQ7 levels (PMID 26081641)

Created: 13 Nov 2018, 1:32 p.m.

Green List (high evidence)

Seizures are a prominent feature.

Created: 12 Aug 2018, 2:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Coenzyme Q10 deficiency, primary, 5, MIM#614654

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