Human GRIN2B variants in neurodevelopmental disorders.
The development of whole exome/genome sequencing technologies has given rise to an unprecedented volume of data linking patient genomic variability to brain disorder phenotypes. A surprising number of variants have been found in the N-methyl-d-aspartate receptor (NMDAR) gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental delay, epilepsy, and schizophrenia. The GRIN2B gene plays a crucial role in normal neuronal development and is important for learning and memory. Mutations in human GRIN2B were distributed throughout the entire gene in a number of patients with various neuropsychiatric and developmental disorders. Studies that provide functional analysis of variants are still lacking, however current analysis of de novo variants that segregate with disease cases such as intellectual disability, developmental delay, ASD or epileptic encephalopathies reveal altered NMDAR function. Here, we summarize the current reports of disease-associated variants in GRIN2B from patients with multiple neurodevelopmental disorders, and discuss implications, highlighting the importance of functional analysis and precision medicine therapies.
Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA.
Chun
C
Hu
Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA.
Wenjuan
W
Chen
Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA; Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA.
Scott J
SJ
Myers
Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA; Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA.
Hongjie
H
Yuan
Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA; Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA. Electronic address: strayne@emory.edu.
Stephen F
SF
Traynelis
D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D065886:Neurodevelopmental Disorders / Q000175:diagnosis / Q000235:genetics*; D017433:Protein Structure, Secondary; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics*
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate
Developmental delay; GluN2B/NR2B; Intellectual disability; NMDA receptor; Neuropsychiatric disorders