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Author Notes:

Corresponding Author: Stephen F. Traynelis Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA. Fax: +1 404 727 0365. Email: strayne@emory.edu

We thank Dr. Sharon A. Swanger for critical comments on the manuscript.

S.F.T is a cofounder of NeurOp Inc., and a paid consultant of NeurOp Inc, Janssen Pharmaceuticals, and Pfizer Inc.

Subjects:

Research Funding:

This work was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (R01HD082373 to H.Y), the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR000454 to H.Y), and the National Institute of Neurological Disorders and Stroke (NS036654 to S.F.T.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Pharmacology & Pharmacy
  • NMDA receptor
  • GluN2B/NR2B
  • Neuropsychiatric disorders
  • Developmental delay
  • Intellectual disability
  • DE-NOVO MUTATIONS
  • AUTISM SPECTRUM DISORDERS
  • NMDA RECEPTOR SUBUNITS
  • INTELLECTUAL DISABILITY
  • PDZ PROTEINS
  • C-TERMINUS
  • ASSOCIATION
  • SCHIZOPHRENIA
  • IMPAIRMENT
  • EXPRESSION

Human GRIN2B variants in neurodevelopmental disorders

Tools:

Journal Title:

Journal of Pharmacological Sciences

Volume:

Volume 132, Number 2

Publisher:

, Pages 115-121

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© 2016 The Authors

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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