Chromosome 12p deletion spanning the GRIN2B gene presenting with a neurodevelopmental phenotype: A case report and review of literature

Original research article by N. Mishra et al. (2016)

Read the abstract here.

The GRIN2B gene plays an important role in brain formation and development, so changes in this gene can significantly impact a child’s development and brain activity. The authors studied one child with a loss-of-function GRIN2B change (the gene lost the ability to perform a normal function), which was not found in either parent (de novo), and they compared this child’s clinical features and genetic change with cases studied by other researchers. This child was a 3-year-old boy with global developmental delay that impacted his motor and language skills. He also had minor differences in facial features, moderate intellectual disability, and muscle weakness. He did not have a history of seizures.

Combining information from other case studies with their own, the researchers summarized effects of the GRIN2B changes in 13 people. These people ranged from ages 2 to 24, and nine of them had de novo loss-of-function changes. These nine people had clinical features similar to those of the child who was the focus of this study. Of the remaining four people, three had de novo gain-of-function GRIN2B changes (the gene gained an abnormal function) and one had a GRIN2B change inherited from his father. These four people had varying degrees of intellectual disability, abnormal brain activity (identified on EEG), muscle spasms, and seizures. The researchers observed that GRIN2B loss-of-function changes were associated with developmental delay, and gain-of-function changes were associated with epilepsy. Both types of changes are also associated with autism spectrum disorder and schizophrenia.

Features Observed Number of Individuals Affected
Individuals with Loss-of-Function GRIN2B Mutations Developmental delay (motor and speech skills) 7/9
Differences in facial features 3/9
Behavioral problems 6/9
Muscle weakness (hypotonia) 2/9
Intellectual Disability (ID) 9/9

(3 Mild ID, 5 Moderate ID, 1 Severe ID)

Individuals with Gain-of-Function GRIN2B Mutations and Individual with “Other” GRIN2B Mutation Diagnosed seizure disorder (West syndrome) 3/4
Abnormal brain activity (via EEG) 4/4
Intellectual Disability (ID) 4/4

(1 Mild ID, 3 Severe ID)