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GRIN2A Variant in A 3-Year-Old—An Expanding Spectrum?
Glutamate, the major excitatory neurotransmitter, plays a ubiquitous role in most aspects of normal brain functioning. Its indispensable position is paradoxically doubled by a high excitotoxic potential following disruption of its dynamic equilibrium. Several lines of evidence have suggested the inv...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163151/ https://www.ncbi.nlm.nih.gov/pubmed/33946630 http://dx.doi.org/10.3390/neurolint13020018 |
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author | Gheța, Ioana Teleanu, Raluca Ioana Roza, Eugenia Carapancea, Evelina Vladacenco, Oana Teleanu, Daniel Mihai |
author_facet | Gheța, Ioana Teleanu, Raluca Ioana Roza, Eugenia Carapancea, Evelina Vladacenco, Oana Teleanu, Daniel Mihai |
author_sort | Gheța, Ioana |
collection | PubMed |
description | Glutamate, the major excitatory neurotransmitter, plays a ubiquitous role in most aspects of normal brain functioning. Its indispensable position is paradoxically doubled by a high excitotoxic potential following disruption of its dynamic equilibrium. Several lines of evidence have suggested the involvement of the glutamatergic N-methyl-D-aspartate receptor (NMDAR) in learning, memory formation, and human cognition. Furthermore, NMDARs play a pivotal role in various neuropsychiatric disorders, recently being identified as an important locus for disease-associated genomic variation. The GRIN2A gene encodes the NMDAR’s GluN2A subunit. Genetic alterations of GRIN2A result in phenotypic pleiotropy, predisposing to a broad range of epilepsy syndromes, with an elusive and unpredictable evolution and response to treatment. The archetypal GRIN2A-related phenotype comprises the idiopathic focal epilepsies (IFEs), with a higher incidence of GRIN2A mutants among entities at the more severe end of the spectrum. We report the case of a patient heterozygous for GRIN2A, c.1081C>T, presenting with febrile convulsions and later superimposed atonic seizures, expressive language delay, and macrocephaly. As the number of reported GRIN2A variants is continuously increasing, the phenotypic boundaries gradually grow faint. Therefore, it is fundamental to maintain an acute critical awareness of the possible genetic etiology of different epilepsy syndromes. So far, therapeutic strategies rely on empirical observations relating genotypes to specific drugs, but the overall success of treatment remains unpredictable. Deciphering the functional consequences of individual GRIN2A variants could lead to the development of precision therapeutic approaches for patients carrying NMDAR mutations. |
format | Online Article Text |
id | pubmed-8163151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81631512021-05-29 GRIN2A Variant in A 3-Year-Old—An Expanding Spectrum? Gheța, Ioana Teleanu, Raluca Ioana Roza, Eugenia Carapancea, Evelina Vladacenco, Oana Teleanu, Daniel Mihai Neurol Int Case Report Glutamate, the major excitatory neurotransmitter, plays a ubiquitous role in most aspects of normal brain functioning. Its indispensable position is paradoxically doubled by a high excitotoxic potential following disruption of its dynamic equilibrium. Several lines of evidence have suggested the involvement of the glutamatergic N-methyl-D-aspartate receptor (NMDAR) in learning, memory formation, and human cognition. Furthermore, NMDARs play a pivotal role in various neuropsychiatric disorders, recently being identified as an important locus for disease-associated genomic variation. The GRIN2A gene encodes the NMDAR’s GluN2A subunit. Genetic alterations of GRIN2A result in phenotypic pleiotropy, predisposing to a broad range of epilepsy syndromes, with an elusive and unpredictable evolution and response to treatment. The archetypal GRIN2A-related phenotype comprises the idiopathic focal epilepsies (IFEs), with a higher incidence of GRIN2A mutants among entities at the more severe end of the spectrum. We report the case of a patient heterozygous for GRIN2A, c.1081C>T, presenting with febrile convulsions and later superimposed atonic seizures, expressive language delay, and macrocephaly. As the number of reported GRIN2A variants is continuously increasing, the phenotypic boundaries gradually grow faint. Therefore, it is fundamental to maintain an acute critical awareness of the possible genetic etiology of different epilepsy syndromes. So far, therapeutic strategies rely on empirical observations relating genotypes to specific drugs, but the overall success of treatment remains unpredictable. Deciphering the functional consequences of individual GRIN2A variants could lead to the development of precision therapeutic approaches for patients carrying NMDAR mutations. MDPI 2021-04-29 /pmc/articles/PMC8163151/ /pubmed/33946630 http://dx.doi.org/10.3390/neurolint13020018 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Case Report Gheța, Ioana Teleanu, Raluca Ioana Roza, Eugenia Carapancea, Evelina Vladacenco, Oana Teleanu, Daniel Mihai GRIN2A Variant in A 3-Year-Old—An Expanding Spectrum? |
title | GRIN2A Variant in A 3-Year-Old—An Expanding Spectrum? |
title_full | GRIN2A Variant in A 3-Year-Old—An Expanding Spectrum? |
title_fullStr | GRIN2A Variant in A 3-Year-Old—An Expanding Spectrum? |
title_full_unstemmed | GRIN2A Variant in A 3-Year-Old—An Expanding Spectrum? |
title_short | GRIN2A Variant in A 3-Year-Old—An Expanding Spectrum? |
title_sort | grin2a variant in a 3-year-old—an expanding spectrum? |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163151/ https://www.ncbi.nlm.nih.gov/pubmed/33946630 http://dx.doi.org/10.3390/neurolint13020018 |
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