Early onset or syndromic epilepsy

Gene: GTPBP3

I don't know

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 there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Kept rating as Amber.

Created: 25 Nov 2019, 8:42 p.m. | Last Modified: 25 Nov 2019, 8:43 p.m.

Panel Version: 1.436

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene can remain as Amber: GTPBP3 is Green on the 'Inborn errors of metabolism' panel (467) so will be Green on the Epilepsy Super panel (489).

Created: 13 Aug 2019, 4:19 p.m. | Last Modified: 13 Aug 2019, 4:19 p.m.

Panel Version: 1.217

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: 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)

The majority of disease-causing variants in this gene have come from a single source publication, PMID 25434004, and are associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy which can be associated with seizures.

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
Combined oxidative phosphorylation deficiency 23, 616198

Publications

• 25434004

Comment when marking as ready: GTPBP3 remains an amber gene as there are only 2 reported cases of epilepsy for this gene. I have put the 'watchlist' tag on so that if new cases appear this gene will be updated accordingly.

Created: 3 Dec 2018, 10:32 a.m.

Comment when marking as ready: Associated with 'mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy' in Gene2phenotype and associated with 'Combined oxidative phosphorylation deficiency 23' in OMIM. OMIM also states that some patients suffer from seizures. However, only 2 unrelated families with different variants in GTPBP3 have been reported to have seizures (PMID: 25434004). In OMIM it has stated that seizures is a less common phenotype of the disease.

Created: 13 Nov 2018, 4:57 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 14 Aug 2018, 11:16 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 23, MIM#616198

Publications

• 25434004

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