Intellectual disability syndromic and non-syndromic
Gene: GRIN2A

GRIN2A (glutamate ionotropic receptor NMDA type subunit 2A)
EnsemblGeneIds (GRCh38): ENSG00000183454
EnsemblGeneIds (GRCh37): ENSG00000183454
OMIM: 138253, Gene2Phenotype
GRIN2A is in 8 panels

2 reviews

Teresa Zhao (Victorian Clinical Genetics Services)

Green List (high evidence)

An 8yo girl with severe developmental and epileptic encephalopathy with two GRIN2A variants in trans (p.Q661* and p.L830Pfs*2). Functional investigations of both variants suggested a loss-of-function effect.

Proband and affected mother both have epilepsy. Epilepsy is suspected in her brother , but an EEG at 10 years remained unremarkable. Genetic testing has not been performed.

Proband and affected parents all have ID and/or DD.
Created: 1 Sep 2022, 6:35 a.m. | Last Modified: 1 Sep 2022, 6:35 a.m.

Panel Version: 0.4912

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, focal, with speech disorder and with or without mental retardation (MIM#245570)

Publications

PMID: 35983985

Created: 1 Sep 2022, 6:35 a.m.
Last Modified: 1 Sep 2022, 6:35 a.m.
Panel version: 0.4912

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Large cohort of 248 individuals reported in PMID: 30544257: The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. Pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes. Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function.
Created: 21 Apr 2020, 2:35 a.m. | Last Modified: 21 Apr 2020, 2:35 a.m.

Panel Version: 0.2566

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy, focal, with speech disorder and with or without mental retardation, MIM# 245570

Publications

30544257

Mode of pathogenicity
Other

Created: 21 Apr 2020, 2:35 a.m.
Last Modified: 21 Apr 2020, 2:35 a.m.
Panel version: 0.2566

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

Epilepsy, focal, with speech disorder and with or without mental retardation, MIM# 245570

OMIM

138253

Clinvar variants

Variants in GRIN2A

Penetrance

None

Publications

Mode of Pathogenicity

Other

Panels with this gene