| Autoři |
GHAFFAR Amama
AKHTER Tehmeena
STROMME Petter
MISCEO Doriana
KHAN Amjad
FRENGEN Eirik
UMAIR Muhammad
ISIDOR Bertrand
COGNE Benjamin
KHAN Asma A
BRUEL Ange-Line
SORLIN Arthur
KUENTZ Paul
CHIAVERINI Christine
INNES A Micheil
ZECH Michael
BALÁŽ Marek
HAVRANKOVA Petra
JECH Robert
AHMED Zubair M
RIAZUDDIN Sheikh
RIAZUDDIN Saima
|
| Rok publikování |
2024 |
| Druh |
Článek v odborném periodiku
|
| Časopis / Zdroj |
Communications Biology |
| Fakulta / Pracoviště MU |
Lékařská fakulta
|
| Citace |
GHAFFAR, Amama, Tehmeena AKHTER, Petter STROMME, Doriana
MISCEO, Amjad KHAN, Eirik FRENGEN, Muhammad UMAIR, Bertrand
ISIDOR, Benjamin COGNE, Asma A KHAN, Ange-Line BRUEL, Arthur
SORLIN, Paul KUENTZ, Christine CHIAVERINI, A Micheil INNES,
Michael ZECH, Marek BALÁŽ, Petra HAVRANKOVA, Robert JECH,
Zubair M AHMED, Sheikh RIAZUDDIN a Saima RIAZUDDIN. Variants of
NAV3, a neuronal morphogenesis protein, cause intellectual
disability, developmental delay, and microcephaly.
Communications Biology. BERLIN: Nature Research, 2024, roč. 7,
č. 1, s. 1-13. ISSN 2399-3642. Dostupné z:
https://dx.doi.org/10.1038/s42003-024-06466-1. |
| www |
https://www.nature.com/articles/s42003-024-06466-1
|
| Doi |
http://dx.doi.org/10.1038/s42003-024-06466-1 |
| Klíčová slova |
NAV3
|
| Přiložené soubory |
|
| Popis |
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.
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