Overlapping cortical malformations in patients with pathogenic variants in GRIN1 and GRIN2B
| Autor: | Stefanie Brock, Annie Laquerriere, Florent Marguet, Scott J Myers, Yuan Hongjie, Diana Baralle, Tim Vanderhasselt, Katrien Stouffs, Kathelijn Keymolen, Sukhan Kim, James Allen, Gil Shaulsky, Jamel Chelly, Pascale Marcorelle, Jacqueline Aziza, Laurent Villard, Elise Sacaze, Marie C Y de Wit, Martina Wilke, Grazia Maria Simonetta Mancini, Ute Hehr, Derek Lim, Sahar Mansour, Stephen F Traynelis, Claire Beneteau, Marie Denis-Musquer, Anna C Jansen, Andrew E Fry, Nadia Bahi-Buisson |
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| Přispěvatelé: | Neurology, Clinical Genetics, Internal Medicine, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Journal of medical genetics Journal of Medical Genetics, 60(2), 183-192. BMJ Publishing Group Journal of Medical Genetics Journal of Medical Genetics, 2022, pp.jmedgenet-2021-107971. ⟨10.1136/jmedgenet-2021-107971⟩ |
| ISSN: | 0022-2593 1468-6244 |
| Popis: | BackgroundMalformations of cortical development (MCDs) have been reported in a subset of patients with pathogenic heterozygous variants inGRIN1orGRIN2B, genes which encode for subunits of the N-methyl-D-aspartate receptor (NMDAR). The aim of this study was to further define the phenotypic spectrum of NMDAR-related MCDs.MethodsWe report the clinical, radiological and molecular features of 7 new patients and review data on 18 previously reported individuals with NMDAR-related MCDs. Neuropathological findings for two individuals with heterozygous variants inGRIN1are presented. We report the clinical and neuropathological features of one additional individual with homozygous pathogenic variants inGRIN1.ResultsHeterozygous variants inGRIN1andGRIN2Bwere associated with overlapping severe clinical and imaging features, including global developmental delay, epilepsy, diffuse dysgyria, dysmorphic basal ganglia and hippocampi. Neuropathological examination in two fetuses with heterozygousGRIN1variants suggests that proliferation as well as radial and tangential neuronal migration are impaired. In addition, we show that neuronal migration is also impaired by homozygousGRIN1variants in an individual with microcephaly with simplified gyral pattern.ConclusionThese findings expand our understanding of the clinical and imaging features of the ‘NMDARopathy’ spectrum and contribute to our understanding of the likely underlying pathogenic mechanisms leading to MCD in these patients. |
| Databáze: | OpenAIRE |
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