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Spectrum of NMDA Receptor Variants in Neurodevelopmental Disorders and Epilepsy

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NMDA Receptors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2799))

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Abstract

N-methyl-D-aspartate receptors (NMDAR) are ligand-gated ion channels mediating excitatory neurotransmission and are important for normal brain development, cognitive abilities, and motor functions. Pathogenic variants in the Glutamate receptor Ionotropic N-methyl-D-aspartate (GRIN) genes (GRIN1, GRIN2A-D) encoding NMDAR subunits have been associated with a wide spectrum of neurodevelopmental disorders and epilepsies ranging from treatable focal epilepsies to devastating early-onset developmental and epileptic encephalopathies. Genetic variants in NMDA receptor genes can cause a range of complex alterations to receptor properties resulting in various degrees of loss-of-function, gain-of-function, or mixtures thereof. Understanding how genetic variants affect the function of the receptors, therefore, represents an important first step in the ongoing development towards targeted therapies. Currently, targeted treatment options for GRIN-related diseases are limited. However, treatment with memantine has been reported to significantly reduce seizure frequency in a few individuals with developmental and epileptic encephalopathies harboring de novo gain-of-function GRIN2A missense variants, and supplementary treatment with L-serine has been associated with improved motor and cognitive performance as well as reduced seizure frequency in patients with GRIN2B loss-of-function missense variants as well as GRIN2A and GRIN2B null variants.

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Author information

Authors and Affiliations

  1. Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark

    Cathrine E. Gjerulfsen, Guido Rubboli & Rikke S. Møller

  2. Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

    Ilona Krey, Chiara Klöckner & Johannes R. Lemke

  3. Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Guido Rubboli

  4. Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

    Rikke S. Møller

Authors
  1. Cathrine E. Gjerulfsen
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  2. Ilona Krey
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  3. Chiara Klöckner
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  4. Guido Rubboli
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  5. Johannes R. Lemke
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  6. Rikke S. Møller
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Corresponding author

Correspondence to Rikke S. Møller .

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Editors and Affiliations

  1. INSERM, Aix-Marseille University, Mediterranean Institute of Neurobiology (INMED), Marseille, France

    Nail Burnashev

  2. INSERM, Aix-Marseille University, Mediterranean Institute of Neurobiology (INMED), Marseille, France

    Pierre Szepetowski

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© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Gjerulfsen, C.E., Krey, I., Klöckner, C., Rubboli, G., Lemke, J.R., Møller, R.S. (2024). Spectrum of NMDA Receptor Variants in Neurodevelopmental Disorders and Epilepsy. In: Burnashev, N., Szepetowski, P. (eds) NMDA Receptors. Methods in Molecular Biology, vol 2799. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3830-9_1

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  • DOI: https://doi.org/10.1007/978-1-0716-3830-9_1

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3829-3

  • Online ISBN: 978-1-0716-3830-9

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