Early onset or syndromic epilepsy

Gene: GRIA4

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)

possible dominant functional effect, not simply loss of function. AD neurodevelopmental disorder with or without seizures and gait abnormalities. Global dev delay apparent from infancy/early childhood. Some patients may develop seizures of variabled severity ealy in life. Martin et al, 2017 - 5 unrelated patients aged 4-21. 1 patient had developed intractable seizures at 5 weeks of age. 3 of the other 4 had seizures of varying severity. 5 diff de novo het missense variants detected. 4/5 in a highly conserved motif. No functional studies undertaken but molecular modelling suggest these mutations would disturbthe gating mech. The 5th variant was in the mildest aff patient and thought to interefer with binding between monomers.

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
Neurodevelopmental disorder with or without seizures and gait abnormalities, 617864

Publications

• 29220673

Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. Seizures reported in 3/5 unrelated probands carrying monoallelic variants in GRIA4 (PMID 29220673). Mouse model carrying a GRIA4 variant display absence epilepsy (PMID 18316356).

Created: 25 Sep 2018, 4:37 p.m.

Green List (high evidence)

Five unrelated individuals described with de novo variants in this gene and a neurodevelopment phenotype including seizures.

Created: 16 Aug 2018, 7:02 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder with or without seizures and gait abnormalities, MIM#617864

Publications

• 29220673

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