GRIN2B-related neurodevelopmental disorder – GRIN2B gene 

The GRIN2B-related neurodevelopmental disorder, also known as syndrome related to GRIN2B or encephalopathy GRIN2B, is a condition that affects the nervous system as a consequence of the deterioration of the growth and development of the central nervous system.

Signs and symptoms related to this process can include mild to severe intellectual disability and delay in the development of speech and motor skills; hypotonia and spasticity. In addition, some individuals have epilepsy and characteristics of the autism spectrum disorder or other behavioral problems. Less frequently, this process is associated with structural abnormalities of the brain, microcephaly, impaired vision and involuntary muscle movements.

As its name suggests, this process is due to mutations in the GRIN2B gene (glutamate ionotropic receptor NMDA type subunit 2B), located on the short arm of chromosome 12 (12p13.1), which encodes the GluN2B protein, which is found in neurons of the brain mainly during development before birth. This protein is part of the NMDA receptors, which participate in normal brain development, synaptic plasticity, learning and memory.

Several dozen mutations in the GRIN2B gene have been described in individuals with neurological development impairment related to GRIN2B, many of which result in the synthesis of a non-functional GluN2B protein or inhibit the synthesis of any GluN2B protein from a copy of the gene in each cell. A deficiency of this protein can decrease the number of functional NMDA receptors, which would reduce the receptor activity in the cells. Other mutations result in the synthesis of abnormal GluN2B proteins that probably alter the function of NMDA receptors; some mutations reduce NMDA receptor signaling while others increase it; however, it is not clear how the abnormal activity of NMDA receptors prevents the normal growth and development of the brain.

This process is inherited with an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to express the process. Most cases of this condition occur in people with no history of the disease in their family and are due to new mutations in the gene that occur during the formation of reproductive cells or early embryonic development.

Tests carried out in IVAMI: in IVAMI we perform the detection of mutations associated with the alteration of the neurological development associated with GRIN2B, by means of the complete amplification by PCR of the exons of the GRIN2B gene, and their subsequent sequencing.

Recommended samples: blood drawn with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).