GRIN2A Variant in A 3-Year-Old-An Expanding Spectrum?
| Title: | GRIN2A Variant in A 3-Year-Old-An Expanding Spectrum? |
|---|---|
| Authors: | Gheța I; Department of Pediatric Neurology, 'Dr Victor Gomoiu' Children's Hospital, 22102 Bucharest, Romania.; Teleanu RI; Department of Pediatric Neurology, 'Dr Victor Gomoiu' Children's Hospital, 22102 Bucharest, Romania.; 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.; Roza E; Department of Pediatric Neurology, 'Dr Victor Gomoiu' Children's Hospital, 22102 Bucharest, Romania.; 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.; 'Victor Babes' University of Medicine and Pharmacy, 300041 Timisoara, Romania.; Carapancea E; Department of Pediatric Neurology, 'Dr Victor Gomoiu' Children's Hospital, 22102 Bucharest, Romania.; 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.; Vladacenco O; Department of Pediatric Neurology, 'Dr Victor Gomoiu' Children's Hospital, 22102 Bucharest, Romania.; Teleanu DM; 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania. |
| Source: | Neurology international [Neurol Int] 2021 Apr 29; Vol. 13 (2), pp. 184-189. Date of Electronic Publication: 2021 Apr 29. |
| Publication Type: | Case Reports; Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551564 Publication Model: Electronic Cited Medium: Print ISSN: 2035-8385 (Print) Linking ISSN: 20358385 NLM ISO Abbreviation: Neurol Int Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Publication: 2020- : Basel, Switzerland : MDPI; Original Publication: Pavia, Italy : PagePress |
| Abstract: | 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. |
| References: | Epileptic Disord. 2019 Jun 1;21(S1):41-47. (PMID: 31149903); J Neurosci. 2008 Apr 2;28(14):3623-30. (PMID: 18385321); Brain. 2019 Jan 1;142(1):80-92. (PMID: 30544257); J Gen Physiol. 2018 Aug 6;150(8):1081-1105. (PMID: 30037851); Mov Disord. 2018 Jul;33(6):992-999. (PMID: 29644724); PLoS One. 2017 Feb 9;12(2):e0170818. (PMID: 28182669); Nature. 2016 Aug 17;536(7616):285-91. (PMID: 27535533); Epilepsy Res. 2015 Sep;115:95-9. (PMID: 26220384); Lancet Neurol. 2011 Jan;10(1):63-74. (PMID: 21163445); J Neurol. 2011 Jan;258(1):27-33. (PMID: 20658246); Cell Rep. 2020 Sep 1;32(9):108104. (PMID: 32877683); Neurosci Bull. 2018 Jun;34(3):549-565. (PMID: 29124671); Nat Genet. 2013 Sep;45(9):1073-6. (PMID: 23933818); J Pediatr Genet. 2020 Dec;9(4):252-257. (PMID: 32765929); Pharmacol Res Perspect. 2019 Jun 20;7(4):e00495. (PMID: 31249692); Epilepsy Res. 2020 Jul;163:106325. (PMID: 32289570); Pediatr Neurol. 2009 Jul;41(1):59-64. (PMID: 19520279); Eur J Paediatr Neurol. 2017 May;21(3):530-541. (PMID: 28109652); Int J Mol Sci. 2020 Feb 24;21(4):. (PMID: 32102377); Neuron. 1998 Jun;20(6):1067-71. (PMID: 9655495); Brain Dev. 2018 Mar;40(3):205-210. (PMID: 29056244); Epilepsy Res. 2019 May;152:18-30. (PMID: 30870728); Br J Pharmacol. 2017 Jan;174(2):119-125. (PMID: 27771943); Brain. 2020 Jul 1;143(7):2039-2057. (PMID: 32577763); Cell Res. 2015 Jul;25(7):818-36. (PMID: 26088419); Am J Hum Genet. 2016 Dec 1;99(6):1261-1280. (PMID: 27839871); Ann Clin Transl Neurol. 2014 Mar 1;1(3):190-198. (PMID: 24839611) |
| Contributed Indexing: | Keywords: GRIN2A gene; N-methyl-D-aspartate receptor (NMDAR); child; genetic epilepsy |
| Entry Date(s): | Date Created: 20210505 Latest Revision: 20210601 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8163151 |
| DOI: | 10.3390/neurolint13020018 |
| PMID: | 33946630 |
| Database: | MEDLINE |
Case Reports; Journal Article