Alternate gene names: NR2A, NMDAR2A
Associated syndromes or conditions: Epilepsy, speech disorders
Genomic location: 16p13.2
Diagnoses observed in people with changes in the GRIN2A gene:
- Autism Spectrum Disorder – yes
- Intellectual Disability or Developmental Delay – yes
- Epilepsy or Seizures – yes
- Attention Deficit Hyperactivity Disorder – no
- Schizophrenia – no
- Bipolar Disorder – no
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Research Article Summaries:
Below, we've summarized several research articles that include information about GRIN2A. We hope you find this information helpful! As we learn more from children who have these gene changes, we expect this list of resources and information to grow.
- Pierson TM et al., (2014) – GRIN2A mutation and early-onset epileptic encephalopathy: personalized therapy with memantine
The GRIN2A gene encodes for proteins that are linked to signaling pathways in the brain. These proteins have a big role in brain development, learning and memory, and signaling within the brain. GRIN2A has been associated with diagnoses of epilepsy, developmental delay, and intellectual disability.
In this article, researchers detail one individual identified to have a de novo mutation (genetic change not found in either parent) in the GRIN2A gene. Identified through the National Institutes of Health (NIH) Undiagnosed Diseases program, the six-year-old boy had a history of early-onset epileptic encephalopathy and profound global developmental delay, having not reached any developmental milestones. He was reported to have daily seizures that did not respond to medication. His brain MRI showed a loss of volume and grey matter (brain tissue).
The researchers suggest that this mutation has hindered the ability of the proteins associated with GRIN2A to function properly, leading to seizures, abnormal development, and brain abnormalities. Research such as this can be helpful to both researchers and clinicians. This study suggests that it may be reasonable to consider a broad genetic test, like whole exome sequencing, to include analysis of genes not typically included in targeted panels.
DeVries SP and Patel AD, (2013)– Two patients with a GRIN2A mutation and childhood-onset epilepsy
Neurotransmitters are chemicals that aid in signaling between nerve cells in the brain. Genetic changes, or mutations, in GRIN2A can have an impact on neurotransmitter function and have been linked to childhood-onset epilepsy with varying degrees of severity, as well as autism and other neurological disorders. In this paper, Drs. DeVries and Patel describe the clinical features of two patients identified to have mutations in the GRIN2A gene.
Patient #1 was a 3-year-old boy with global developmental delay. It was reported that he experienced his first seizure at the age of two. An EEG revealed abnormalities and, through microarray testing, he was found to have a deletion of most of the GRIN2A gene. He had a wide gait (walking pattern) and was reported as being seizure-free for six months with the help of medication. After 6 months, he developed seizures again, and was unsteady on his feet. After adjustments in medication dosages and a rigorous physical therapy regimen, he once again became seizure-free and experienced an improvement in walking. Patient #1’s mother also had a history of childhood-onset seizures, and was found to have the same mutation as her son.
Patient #2 was a 9-year-old boy who experienced multiple seizure types beginning at age 4. He experienced over 100 seizures a day and numerous medications and treatments failed to improve his seizure frequency. Through whole exome sequencing, he was found to have a GRIN2A mutation. His development was initially reported to be normal, but declined at age 4, after his seizures began. Patient #2’s father was found to have the same mutation. He did not report a history of seizures, but did have a history of major depressive disorder. See below for a comparison of both patients’ clinical features.
These case studies, as well as other literature, show that individuals with a mutation in the GRIN2A gene can have a wide-spectrum of clinical features, including seizures. This research suggests that in the future, GRIN2A may be considered when developing genetic tests targeted on childhood-onset epilepsy.
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