Brock, Stefanie and Laquerriere, Annie and Marguet, Florent and Myers, Scott J. and Hongjie, Yuan and Baralle, Diana and Vanderhasselt, Tim and Stouffs, Katrien and Keymolen, Kathelijn and Kim, Sukhan and Allen, James and Shaulsky, Gil and Chelly, Jamel and Marcorelle, Pascale and Aziza, Jacqueline and Villard, Laurent and Sacaze, Elise and de Wit, Marie C. Y. and Wilke, Martina and Mancini, Grazia Maria Simonetta and Hehr, Ute and Lim, Derek and Mansour, Sahar and Traynelis, Stephen F. and Beneteau, Claire and Denis-Musquer, Marie and Jansen, Anna C. and Fry, Andrew E. and Bahi-Buisson, Nadia (2023) Overlapping cortical malformations in patients with pathogenic variants in GRIN1 and GRIN2B. JOURNAL OF MEDICAL GENETICS, 60 (2). pp. 183-192. ISSN 0022-2593, 1468-6244
Full text not available from this repository. (Request a copy)Abstract
Background Malformations of cortical development (MCDs) have been reported in a subset of patients with pathogenic heterozygous variants in GRIN1 or GRIN2B, 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. Methods We 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 in GRIN1 are presented. We report the clinical and neuropathological features of one additional individual with homozygous pathogenic variants in GRIN1. Results Heterozygous variants in GRIN1 and GRIN2B were 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 heterozygous GRIN1 variants suggests that proliferation as well as radial and tangential neuronal migration are impaired. In addition, we show that neuronal migration is also impaired by homozygous GRIN1 variants in an individual with microcephaly with simplified gyral pattern. Conclusion These 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTELLECTUAL DISABILITY; FUNCTIONAL CONSEQUENCES; RARE VARIANTS; MUTATIONS; SUBUNIT; ENCEPHALOPATHY; STANDARDS; MIGRATION; IBOTENATE; MODEL; Nervous System Malformations; Genetics; Pathology; Radiology; Pediatrics |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Mar 2024 14:20 |
| Last Modified: | 05 Mar 2024 14:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58753 |
Actions (login required)
 |
View Item |
