Early onset or syndromic epilepsy

Gene: GNAQ

PMID: 34124757, Fjaer et al 2021 reports a further 5 cases in which the GNAQ:c.548G>A (R183Q) somatic mutation was found in dermal biopsies in patients with Sturge–Weber syndrome-associated features. Seizures are reported in all 5 patients. But note that this mutation is somatic mosaic and not all tested tissues/cultures were positive for the mutation (blood not tested).

Created: 3 Nov 2021, 2:36 p.m. | Last Modified: 3 Nov 2021, 2:36 p.m.

Panel Version: 2.453

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Sturge-Weber syndrome, somatic, mosaic, OMIM:185300

Publications

• 34124757

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. 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)

GNAQ mutation c.548G4A (pR183Q) is possibly gain of function and mosaic in the majority of cases. cerebral vascular malformations result in neurological impairment including seizures BUT would this be detectable by WGS? (read depth is likely to be insufficient and the wrong tissue type is likely to be tested).

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

Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Capillary malformations, congenital, 1, somatic, mosaic 163000; Sturge-Weber syndrome, somatic, mosaic 185300

Publications

• 28454448

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments

Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least one variant (rs397514698) was identified in at least 12/15 cases of Sturge-Weber syndrome, somatic, mosaic, 185300 (PMID 25374402). The percentage of the gain of function variant in brain tissues of these 12 patients ranged from 3.6 to 8.9%.

Created: 6 Dec 2018, 2:26 p.m.

Comment on mode of pathogenicity: Somatic gain of function

Created: 6 Dec 2018, 1:32 p.m.

I don't know

Mutations are somatic, so although seizures are part of the phenotype, I'm not sure whether it is helpful to include in this panel.

Created: 14 Aug 2018, 10:58 a.m.

Mode of inheritance
Other

Phenotypes
Sturge-Weber syndrome, somatic, mosaic, MIM#185300