Editing Charcot–Marie–Tooth disease (section)

=== X-linked CMT ===
Main article: [[X-linked Charcot–Marie–Tooth disease]]

CMT can also be produced by X-linked mutations, in which case it is called X-linked CMT (CMTX). In CMTX, mutated [[Connexon|connexons]] create nonfunctional [[Gap junction|gap junctions]] that interrupt molecular exchange and signal transport.<ref name=":3">{{Cite journal |last1=Berger |first1=Philipp |last2=Young |first2=Peter |last3=Suter |first3=Ueli |date=2002-03-01 |title=Molecular cell biology of Charcot-Marie-Tooth disease |url=https://link.springer.com/article/10.1007/s10048-002-0130-z |journal=Neurogenetics |language=en |volume=4 |issue=1 |pages=1–15 |doi=10.1007/s10048-002-0130-z |pmid=12030326 |issn=1364-6745}}</ref><ref>{{Cite journal |last=Kleopa |first=Kleopas A. |date=2011-12-07 |title=The Role of Gap Junctions in Charcot-Marie-Tooth Disease |url=https://www.jneurosci.org/content/31/49/17753 |journal=Journal of Neuroscience |language=en |volume=31 |issue=49 |pages=17753–17760 |doi=10.1523/JNEUROSCI.4824-11.2011 |issn=0270-6474 |pmid=22159091|pmc=6634164 }}</ref><ref>{{Cite journal |last1=Szigeti |first1=Kinga |last2=Lupski |first2=James R. |date=June 2009 |title=Charcot-Marie-Tooth disease |journal=European Journal of Human Genetics |volume=17 |issue=6 |pages=703–710 |doi=10.1038/ejhg.2009.31 |issn=1476-5438 |pmc=2947101 |pmid=19277060}}</ref>The mutation can appear in the ''[[GJB1]]'' gene coding for the [[connexin 32]] protein, a gap junction protein expressed in Schwann cells. Because this protein is also present in [[oligodendrocytes]], demyelination can appear in the CNS as well.<ref>{{Cite journal |last1=Koutsis |first1=Georgios |last2=Breza |first2=Marianthi |last3=Velonakis |first3=Georgios |last4=Tzartos |first4=John |last5=Kasselimis |first5=Dimitrios |last6=Kartanou |first6=Chrisoula |last7=Karavasilis |first7=Efstratios |last8=Tzanetakos |first8=Dimitrios |last9=Anagnostouli |first9=Maria |last10=Andreadou |first10=Elisavet |last11=Evangelopoulos |first11=Maria-Eleftheria |last12=Kilidireas |first12=Constantinos |last13=Potagas |first13=Constantin |last14=Panas |first14=Marios |last15=Karadima |first15=Georgia |date=2019-02-01 |title=X linked Charcot-Marie-Tooth disease and multiple sclerosis: emerging evidence for an association |url=https://jnnp.bmj.com/content/90/2/187 |journal=Journal of Neurology, Neurosurgery & Psychiatry |language=en |volume=90 |issue=2 |pages=187–194 |doi=10.1136/jnnp-2018-319014 |issn=0022-3050 |pmid=30196252}}</ref>

[[Schwann cell]]s create the myelin sheath by wrapping their plasma membranes around the axon.<ref name=":3" /> These Schwann cells work together with neurons and [[fibroblast]]s to create a functional nerve. Schwann cells and neurons exchange molecular signals by way of gap junctions that regulate survival and differentiation.<ref>{{Cite journal |last1=Amiott |first1=Elizabeth A. |last2=Lott |first2=Paul |last3=Soto |first3=Jamie |last4=Kang |first4=Peter B. |last5=McCaffery |first5=J. Michael |last6=DiMauro |first6=Salvatore |last7=Abel |first7=E. Dale |last8=Flanigan |first8=Kevin M. |last9=Lawson |first9=Victoria H. |last10=Shaw |first10=Janet M. |date=May 2008 |title=Mitochondrial fusion and function in Charcot-Marie-Tooth type 2A patient fibroblasts with mitofusin 2 mutations |journal=Experimental Neurology |volume=211 |issue=1 |pages=115–127 |doi=10.1016/j.expneurol.2008.01.010 |issn=0014-4886 |pmc=2409111 |pmid=18316077}}</ref>

Demyelinating Schwann cells cause abnormal axon structure and function. They may cause axon degeneration, or they may simply cause axons to malfunction.<ref name="Krajewski" /> The myelin sheath allows nerve cells to conduct signals faster. When the myelin sheath is damaged, however, nerve signals are slower. This can be measured by a common neurological test, [[electromyography]]. When the axon is damaged, the result is a reduced compound muscle [[action potential]].<ref>{{Cite journal |last1=Yiu |first1=Eppie M. |last2=Burns |first2=Joshua |last3=Ryan |first3=Monique M. |last4=Ouvrier |first4=Robert A. |date=2008 |title=Neurophysiologic abnormalities in children with Charcot-Marie-Tooth disease type 1A |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1529-8027.2008.00182.x |journal=Journal of the Peripheral Nervous System |language=en |volume=13 |issue=3 |pages=236–241 |doi=10.1111/j.1529-8027.2008.00182.x |pmid=18844790 |issn=1529-8027}}</ref>