Bi-allelic variants in neuronal cell adhesion molecule cause a neurodevelopmental disorder characterized by developmental delay, hypotonia, neuropathy/spasticity.
NRCAM
hypotonia
neurodevelopmental disease
neuronal cell adhesion molecule
peripheral neuropathy
spasticity
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
03 03 2022
03 03 2022
Historique:
received:
30
05
2021
accepted:
07
01
2022
pubmed:
3
2
2022
medline:
3
5
2022
entrez:
2
2
2022
Statut:
ppublish
Résumé
Cell adhesion molecules are membrane-bound proteins predominantly expressed in the central nervous system along principal axonal pathways with key roles in nervous system development, neural cell differentiation and migration, axonal growth and guidance, myelination, and synapse formation. Here, we describe ten affected individuals with bi-allelic variants in the neuronal cell adhesion molecule NRCAM that lead to a neurodevelopmental syndrome of varying severity; the individuals are from eight families. This syndrome is characterized by developmental delay/intellectual disability, hypotonia, peripheral neuropathy, and/or spasticity. Computational analyses of NRCAM variants, many of which cluster in the third fibronectin type III (Fn-III) domain, strongly suggest a deleterious effect on NRCAM structure and function, including possible disruption of its interactions with other proteins. These findings are corroborated by previous in vitro studies of murine Nrcam-deficient cells, revealing abnormal neurite outgrowth, synaptogenesis, and formation of nodes of Ranvier on myelinated axons. Our studies on zebrafish nrcama
Identifiants
pubmed: 35108495
pii: S0002-9297(22)00004-0
doi: 10.1016/j.ajhg.2022.01.004
pmc: PMC8948158
pii:
doi:
Substances chimiques
Cell Adhesion Molecules
0
Cell Adhesion Molecules, Neuronal
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
518-532Subventions
Organisme : NINDS NIH HHS
ID : R01 NS106298
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007672
Pays : United States
Informations de copyright
Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests C.G.-J. is a full-time employee of the Regeneron Genetics Center and receives stock options as part of compensation. All other authors have no conflicts to declare.
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