Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F24%3A10483193" target="_blank" >RIV/00064165:_____/24:10483193 - isvavai.cz</a>
Alternative codes found
RIV/00159816:_____/24:00081209 RIV/00216224:14110/24:00136689 RIV/00216208:11110/24:10483193
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SNlNN7qL3d" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SNlNN7qL3d</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s42003-024-06466-1" target="_blank" >10.1038/s42003-024-06466-1</a>
Alternative languages
Result language
angličtina
Original language name
Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly
Original language description
Microtubule associated proteins (MAPs) are widely expressed in the central nervous system, and have established roles in cell proliferation, myelination, neurite formation, axon specification, outgrowth, dendrite, and synapse formation. We report eleven individuals from seven families harboring predicted pathogenic biallelic, de novo, and heterozygous variants in the NAV3 gene, which encodes the microtubule positive tip protein neuron navigator 3 (NAV3). All affected individuals have intellectual disability (ID), microcephaly, skeletal deformities, ocular anomalies, and behavioral issues. In mouse brain, Nav3 is expressed throughout the nervous system, with more prominent signatures in postmitotic, excitatory, inhibiting, and sensory neurons. When overexpressed in HEK293T and COS7 cells, pathogenic variants impaired NAV3 ability to stabilize microtubules. Further, knocking-down nav3 in zebrafish led to severe morphological defects, microcephaly, impaired neuronal growth, and behavioral impairment, which were rescued with co-injection of WT NAV3 mRNA and not by transcripts encoding the pathogenic variants. Our findings establish the role of NAV3 in neurodevelopmental disorders, and reveal its involvement in neuronal morphogenesis, and neuromuscular responses. neuron navigator-3 (NAV3) is involved in neuronal morphogenesis, vision, and neuromuscular responses, and the biallelic/mono-allelic variants of NAV3 are causative of a spectrum of neurodevelopmental disorders
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
<a href="/en/project/LX22NPO5107" target="_blank" >LX22NPO5107: National institute for Neurological Research</a><br>
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Communications Biology
ISSN
2399-3642
e-ISSN
2399-3642
Volume of the periodical
7
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
13
Pages from-to
831
UT code for WoS article
001265543500001
EID of the result in the Scopus database
2-s2.0-85197708502