Alternate gene names: NMDAR2B, NR2B
Associated syndromes or conditions: Epileptic encephalopathy, early infantile, 27; Intellectual disability type 6 (formerly called "mental retardation type 6")
Genomic location: 12p12
Diagnoses observed in people with changes in the GRIN2B 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
- GRIN2B: Simons VIP Connect Community - Simons VIP Connect Facebook Group for GRIN2B families
In addition to the opportunity to participate in research with Simons VIP, you may be interested in other opportunities.
- The University of Washington’s Autism Center is performing a study to better understand the medical, learning, and behavioral features of individuals with changes in GRIN2B. Click here to learn more about this opportunity, called the TIGER Study.
Research Article Summaries:
Below, we've summarized several research articles that include information about GRIN2B. 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.
Mishra et al. 2016 – Chromosome 12p deletion spanning the GRIN2B gene presenting with a neurodevelopmental phenotype: A case report and review of literature.
The GRIN2B gene plays an important role in brain formation and development, and thus, changes in this gene (mutations) can significantly impact a child’s development and brain activitiy. Interestingly, different types of GRIN2B mutations are associated with different clinical features. Researchers observed that GRIN2B mutations where the gene lost the ability to perform a normal function (called “loss-of-function” mutations) were associated with developmental delay. On the other hand, GRIN2B mutations where the gene gained an abnormal function (called “gain-of-function” mutations) were associated with epilepsy. Both types of mutations are also associated with autism spectrum disorder (ASD) and schizophrenia.
Mishra et al. studied one child with a loss-of-function GRIN2B mutation not found in either parent (also called a de novo mutation) and compared this child’s clinical features and genetic change to cases studied by other researchers. Their case was a 3-year-old boy exhibiting global developmental delay, impacting his motor and language skills. He also had minor differences in facial features (facial dysmorphism), moderate intellectual disability (ID), and muscle weakness (hypotonia). He did not have a history of seizures.
Combining information from other case studies in addition to their own, the researchers were able to summarize the GRIN2B mutations of 13 individuals. These individuals ranged from ages 2 to 24, and nine individuals were found to have de novo loss-of-function mutations. These nine cases exhibited similar clinical features to Mishra et al.’s case study. Of the remaining four individuals, three had de novo gain-of-function GRIN2B mutations and one had a GRIN2B mutation inherited from his father. These four individuals had varying degrees of intellectual disability (ID), abnormal brain activity (identified on EEG), muscle spasms, and seizures.
- Kenny et al. (2014)
Over 400 individuals with schizophrenia (SZ) and autism spectrum disorder (ASD) were screened for gene changes in 215 possible “risk” genes. A variant in GRIN2B was identified to be de novo (not inherited from either parent) in a sample from an individual with autism. Based on this result and previously reported cases, it is suggested that gene changes in GRIN2B can increase the chance for autism and can contribute to brain function and learning differences.
Freunscht et al. (2013) – Behavioral phenotype in five individuals with de novo mutations within the GRIN2B gene
GRIN2B gene changes are now recognized as a common genetic cause of intellectual disability (ID). Mutations in this gene are thought to occur as frequently as 0.5 – 1% in individuals with ID. Although we understand that intellectual disability has been associated with changes in this gene, we have little information about life skills and other areas of strength and weakness in children with this genetic change.
Researchers used behavioral questionnaires to better understand the behavioral profile of 5 children and adolescents with GRIN2B gene changes. The study team used data from the DBC (Developmental Behavior Checklist) completed by the child’s parent(s) and teacher(s). (These questionnaires are similar to checklists and surveys administered to Simons VIP Connect families).
All five individuals had some level of ID, ranging from mild to severe. Four of the five children walked around two years of age, and one of the five children walked closer to three years of age. None of these five children had a history of seizures, although three have a history of abnormal EEGs.
The authors conclude that, “although specific facial dysmorphism and [birth defects] are usually absent in individuals with GRIN2B mutations, there does seem to be a characteristic behavioral [pattern of features] consisting of ID, hyperactivity, impulsivity and distractibility. Stereotypic and stimulatory behavior, sleeping problems and a friendly but boundless social behavior also appear to be associated features.”
- Lemke et al. (2014)
GRINB2 is a gene that has been identified in patients with intellectual disability, autism spectrum disorders and schizophrenia, and has been considered to be involved with seizures. In this study, 357 patients with epileptic disorders and/or intellectual disability (ID) were evaluated for changes in 50 genes known to be associated with seizures, including GRIN2B. Three patients in this study were found to have genetic changes in GRIN2B, 2 of these patients had unexplained epilepsy, and 1 had ID and childhood onset focal epilepsy.
- O’Roak et al. (2012) - Science
In this study, 2,494 samples from the Simon Simplex Collection (SSC) were used to look for 44 genes that have been associated with autism. The SSC study included children with autism and intellectual disability. This study identified 27 de novo (not inherited from either parent) gene changes in 16 genes, including 4 patients with variants in GRIN2B.
- O’Roak et al. (2012) - Nature
Whole exome sequencing was performed for 209 families (677 individuals) who had participated in the Simons Simplex Collection (SSC). The SSC study included children with autism and intellectual disability. This study identified over 100 new candidate genes related to developmental delay, intellectual disability and/or features of autism. Initially, mutations in only two genes – CHD8 and NTNG1 - were found in more than one person, and further analysis of six specific genes (FOXP1, GRIN2B, LAMC3, SCN1A, FOXP2 and GRIN2A) found additional mutations in three of the genes – GRIN2B, LAMC3 and SCN1A - suggesting that there are many various genetic causes of autism and intellectual disability. Three de novo (not inherited from either parent) damaging variants in GRIN2B were identified in the SSC samples, while no damaging variants were identified in over 3000 control samples.
- Endele et al. (2010)
GRINB2 is a gene that is responsible for transmitting information in the brain. 468 individuals with intellectual disability were screened for a GRIN2B gene change; 4 were identified to have a change in this gene, none were inherited from a parent (all were de novo).
You can also visit SFARI's website to see information for researchers about this gene. SFARIgene: GRIN2B
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