Characterization of molecular mechanisms underlying the axonal Charcot-Marie-Tooth neuropathy caused by MORC2 mutations
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F19%3A10395503" target="_blank" >RIV/00064203:_____/19:10395503 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/19:10395503
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=zba_1vuFur" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=zba_1vuFur</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/hmg/ddz006" target="_blank" >10.1093/hmg/ddz006</a>
Alternative languages
Result language
angličtina
Original language name
Characterization of molecular mechanisms underlying the axonal Charcot-Marie-Tooth neuropathy caused by MORC2 mutations
Original language description
Mutations in MORC2 lead to an axonal form of Charcot-Marie-Tooth (CMT) neuropathy type 2Z. To date, 31 families have been described with mutations in MORC2, indicating that this gene is frequently involved in axonal CMT cases. While the genetic data clearly establish the causative role of MORC2 in CMT2Z, the impact of its mutations on neuronal biology and their phenotypic consequences in patients remains to be clarified. We show that the full-length form of MORC2 is highly expressed in both embryonic and adult human neural tissues and that Morc2 expression is dynamically regulated in both the developing and the maturing murine nervous system. To determine the effect of the most common MORC2 mutations, p.S87L and p.R252W, we used several in vitro cell culture paradigms. Both mutations induced transcriptional changes in patient-derived fibroblasts and when expressed in rodent sensory neurons. These changes were more pronounced and accompanied by abnormal axonal morphology, in neurons expressing the MORC2 p.S87L mutation, which is associated with a more severe clinical phenotype. These data provide insight into the neuronal specificity of the mutated MORC2-mediated phenotype and highlight the importance of neuronal cell models to study the pathophysiology of CMT2Z. (C) The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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/NV16-30206A" target="_blank" >NV16-30206A: Whole genome sequencing and RNA sequencing - a tool for elucidation of the causes of rare types of hereditary neuropathies.</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Human Molecular Genetics
ISSN
0964-6906
e-ISSN
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Volume of the periodical
28
Issue of the periodical within the volume
10
Country of publishing house
GB - UNITED KINGDOM
Number of pages
16
Pages from-to
1629-1644
UT code for WoS article
000475882600005
EID of the result in the Scopus database
2-s2.0-85068493842