PMID- 22771394
OWN - NLM
STAT- MEDLINE
DCOM- 20130423
LR  - 20231213
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1487
DP  - 2012 Dec 3
TI  - How do mutations in GJB1 cause X-linked Charcot-Marie-Tooth disease?
PG  - 198-205
LID - S0006-8993(12)01120-1 [pii]
LID - 10.1016/j.brainres.2012.03.068 [doi]
AB  - The X-linked form of Charcot-Marie-Tooth disease (CMT1X) is the second most 
      common form of hereditary motor and sensory neuropathy. The clinical phenotype is 
      characterized by progressive weakness, atrophy, and sensory abnormalities that 
      are most pronounced in the distal extremities. Some patients have CNS 
      manifestations. Affected males have moderate to severe symptoms, whereas 
      heterozygous females are usually less affected. Neurophysiology shows 
      intermediate slowing of conduction and length-dependent axonal loss. Nerve 
      biopsies show more prominent axonal degeneration than de/remyelination. Mutations 
      in GJB1, the gene that encodes the gap junction (GJ) protein connexin32 (Cx32) 
      cause CMT1X; more than 400 different mutations have been described. Many Cx32 
      mutants fail to form functional GJs, or form GJs with abnormal biophysical 
      properties. Schwann cells and oligodendrocytes express Cx32, and the GJs formed 
      by Cx32 play an important role in the homeostasis of myelinated axons. Animal 
      models of CMT1X demonstrate that loss of Cx32 in myelinating Schwann cells causes 
      a demyelinating neuropathy. Effective therapies remain to be developed. This 
      article is part of a Special Issue entitled Electrical Synapses.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Kleopa, Kleopas A
AU  - Kleopa KA
AD  - Neurology Clinics and Neuroscience Laboratory, The Cyprus Institute of Neurology 
      and Genetics, Nicosia, Cyprus.
FAU - Abrams, Charles K
AU  - Abrams CK
FAU - Scherer, Steven S
AU  - Scherer SS
LA  - eng
GR  - GTB12001/TI_/Telethon/Italy
GR  - R01 NS055284/NS/NINDS NIH HHS/United States
GR  - U54 NS065712/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120706
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Connexins)
SB  - IM
MH  - Animals
MH  - Charcot-Marie-Tooth Disease/*genetics
MH  - Connexins/biosynthesis/*genetics
MH  - Disease Models, Animal
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Mutation/*genetics/*physiology
MH  - Myelin Sheath/metabolism/pathology
MH  - Schwann Cells/metabolism/pathology
MH  - Gap Junction beta-1 Protein
PMC - PMC3488165
MID - NIHMS392667
EDAT- 2012/07/10 06:00
MHDA- 2013/04/24 06:00
PMCR- 2013/12/03
CRDT- 2012/07/10 06:00
PHST- 2011/11/02 00:00 [received]
PHST- 2012/03/24 00:00 [accepted]
PHST- 2012/07/10 06:00 [entrez]
PHST- 2012/07/10 06:00 [pubmed]
PHST- 2013/04/24 06:00 [medline]
PHST- 2013/12/03 00:00 [pmc-release]
AID - S0006-8993(12)01120-1 [pii]
AID - 10.1016/j.brainres.2012.03.068 [doi]
PST - ppublish
SO  - Brain Res. 2012 Dec 3;1487:198-205. doi: 10.1016/j.brainres.2012.03.068. Epub 
      2012 Jul 6.