Overlapping cortical malformations in patients with pathogenic variants in


Journal

Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R

Informations de publication

Date de publication:
02 2023
Historique:
received: 13 05 2021
accepted: 16 03 2022
pubmed: 9 4 2022
medline: 27 1 2023
entrez: 8 4 2022
Statut: ppublish

Résumé

Malformations of cortical development (MCDs) have been reported in a subset of patients with pathogenic heterozygous variants in 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 Heterozygous variants in 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.

Sections du résumé

BACKGROUND
Malformations of cortical development (MCDs) have been reported in a subset of patients with pathogenic heterozygous variants in
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
RESULTS
Heterozygous variants in
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.

Identifiants

pubmed: 35393335
pii: jmedgenet-2021-107971
doi: 10.1136/jmedgenet-2021-107971
pmc: PMC10642159
mid: NIHMS1941580
doi:

Substances chimiques

GRIN1 protein, human 0
Nerve Tissue Proteins 0
Receptors, N-Methyl-D-Aspartate 0
NR2B NMDA receptor 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

183-192

Subventions

Organisme : NICHD NIH HHS
ID : R01 HD082373
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_16035
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R21 AG072142
Pays : United States
Organisme : Department of Health
ID : RP-2016- 07-011
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R35 NS111619
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH127404
Pays : United States

Informations de copyright

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: SFT is principal investigator on research grants from Biogen and Janssen to Emory; a member of the Scientific Advisory Board for Eumentis, Sage Therapeutics, GRIN2B Foundation and CureGRIN Foundation; co-founder of NeurOp and Agrithera; and coinventor on Emory-owned intellectual property.

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Auteurs

Stefanie Brock (S)

Department of Pathology, Universitair Ziekenhuis Brussel, Brussels, Belgium Stefanie.Brock@vub.be.
Neurogenetics Research Group, Reproduction Genetics and Regenerative Medicine Research Cluster, Vrije Universiteit Brussel, Brussels, Belgium.

Annie Laquerriere (A)

Normandy Centre for Genomic and Personalized Medicine, INSERM U1245, Rouen, France.
Department of Pathology, Rouen University Hospital, Rouen, France.

Florent Marguet (F)

Normandy Centre for Genomic and Personalized Medicine, INSERM U1245, Rouen, France.
Department of Pathology, Rouen University Hospital, Rouen, France.

Scott J Myers (SJ)

Department of Pharmacology and Chemical Biology, Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.
Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.

Yuan Hongjie (Y)

Department of Pharmacology and Chemical Biology, Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.
Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.

Diana Baralle (D)

Human Development and Health, University of Southampton, Southampton, UK.

Tim Vanderhasselt (T)

Department of Radiology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.

Katrien Stouffs (K)

Neurogenetics Research Group, Reproduction Genetics and Regenerative Medicine Research Cluster, Vrije Universiteit Brussel, Brussels, Belgium.
Center for Reproduction and Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.

Kathelijn Keymolen (K)

Center for Reproduction and Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.

Sukhan Kim (S)

Department of Pharmacology and Chemical Biology, Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.
Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.

James Allen (J)

Department of Pharmacology and Chemical Biology, Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.
Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.

Gil Shaulsky (G)

Department of Pharmacology and Chemical Biology, Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.
Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.

Jamel Chelly (J)

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U1258, Université de Strasbourg, Strasbourg, France.
Laboratoire de Diagnostic Génétique, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.

Pascale Marcorelle (P)

Service d'Anatomie Pathologique, Centre Hospitalier Universitaire de Brest; Laboratoire Neurosciences de Brest, Université de Brest, Brest, France.

Jacqueline Aziza (J)

Department of Pathology, University Institute for Cancer, Toulouse, France.

Laurent Villard (L)

Inserm, Marseille Medical Genetics Center, Aix-Marseille University, Marseille, France.
Department of Medical Genetics, La Timone Children's Hospital, Marseille, France.

Elise Sacaze (E)

Department of Pediatrics, Centre Hospitalier Universitaire de Brest, Brest, France.

Marie C Y de Wit (MCY)

Department of Pediatric Neurology, ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam, The Netherlands.

Martina Wilke (M)

Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.

Grazia Maria Simonetta Mancini (GMS)

Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.

Ute Hehr (U)

Center for Human Genetics, Universitätsklinikum Regensburg, Regensburg, Germany.

Derek Lim (D)

West Midlands Regional Genetics Service and Birmingham Health Partners, Birmingham Women's and Children's Hospitals NHS Foundation Trust, University of Southampton, Southampton, UK.

Sahar Mansour (S)

SW Thames Regional Genetics Service, University of London St George's Molecular and Clinical Sciences Research Institute, London, UK.

Stephen F Traynelis (SF)

Department of Pharmacology and Chemical Biology, Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.
Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine Atlanta, Atlanta, Georgia, USA.

Claire Beneteau (C)

Département de Génétique, Hôpital Universitaire de Nantes, Nantes, France.
UF de Fœtopathologie et Génétique, CHU Nantes, Nantes, France.

Marie Denis-Musquer (M)

UF de Fœtopathologie et Génétique, CHU Nantes, Nantes, France.
Department of Pathology, CHU Nantes, Nantes, France.

Anna C Jansen (AC)

Pediatric Neurology Unit, Universitair Ziekenhuis Antwerpen, Antwerp, Belgium.

Andrew E Fry (AE)

Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK.
Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.

Nadia Bahi-Buisson (N)

Pediatric Neurology, Necker Enfants Malades Hospital, Université de Paris, Paris, France.
Embryology and Genetics of Congenital Malformations, Institut Imagine (INSERM UMR-1163), Paris, France.

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