PMID- 16775370
OWN - NLM
STAT- MEDLINE
DCOM- 20070315
LR  - 20231213
IS  - 1535-1084 (Print)
IS  - 1535-1084 (Linking)
VI  - 8
IP  - 1-2
DP  - 2006
TI  - Molecular genetics of X-linked Charcot-Marie-Tooth disease.
PG  - 107-22
AB  - The X-linked form of Charcot-Marie-Tooth disease (CMT1X) is the second most 
      common molecularly designated form of hereditary motor and sensory neuropathy. 
      The clinical phenotype is characterized by progressive distal muscle atrophy and 
      weakness, areflexia, and variable sensory abnormalities. Affected males have 
      moderate-to-severe symptoms, whereas heterozygous females are usually mildly 
      affected or even asymptomatic. Several patients also have manifestations of 
      central nervous system involvement or hearing impairment. Electrophysiological 
      and pathological studies of peripheral nerves show evidence of demyelinating 
      neuropathy with prominent axonal degeneration. A large number of mutations in the 
      GJB1 gene encoding the gap junction (GJ) protein connexin32 (Cx32) cause CMT1X. 
      Cx32 is expressed by Schwann cells and oligodendrocytes, as well as by other 
      tissues, and the GJ formed by Cx32 play an important role in the homeostasis of 
      myelinated axons. The reported CMT1X mutations are diverse and affect both the 
      promoter region as well as the coding region of GJB1. Many Cx32 mutants fail to 
      form functional GJ, or form GJ with abnormal biophysical properties. Furthermore, 
      Cx32 mutants are often retained intracellularly either in the endoplasmic 
      reticulum or Golgi in which they could potentially have additional 
      dominant-negative effects. Animal models of CMT1X demonstrate that loss of Cx32 
      in myelinating Schwann cells causes a demyelinating neuropathy. No definite 
      phenotype-genotype correlation has yet been established for CMT1X and effective 
      molecular based therapeutics for this disease, remain to be developed.
FAU - Kleopa, Kleopas A
AU  - Kleopa KA
AD  - Department of Clinical Neurosciences, The Cyprus Institute of Neurology and 
      Genetics, Nicosia, Cyprus. kleopa@cing.ac.cy
FAU - Scherer, Steven S
AU  - Scherer SS
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Neuromolecular Med
JT  - Neuromolecular medicine
JID - 101135365
RN  - 0 (Connexins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Charcot-Marie-Tooth Disease/*genetics/pathology/physiopathology/therapy
MH  - Connexins/genetics/metabolism
MH  - Electrophysiology
MH  - Genetic Diseases, X-Linked/*genetics/pathology/physiopathology/therapy
MH  - Genotype
MH  - Humans
MH  - Molecular Biology
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Myelin Sheath/metabolism
MH  - Peripheral Nerves/pathology/physiopathology
MH  - Phenotype
MH  - Protein Structure, Secondary
MH  - Schwann Cells/metabolism
MH  - Gap Junction beta-1 Protein
RF  - 120
EDAT- 2006/06/16 09:00
MHDA- 2007/03/16 09:00
CRDT- 2006/06/16 09:00
PHST- 2005/07/08 00:00 [received]
PHST- 2005/11/10 00:00 [revised]
PHST- 2005/11/17 00:00 [accepted]
PHST- 2006/06/16 09:00 [pubmed]
PHST- 2007/03/16 09:00 [medline]
PHST- 2006/06/16 09:00 [entrez]
AID - NMM:8:1:107 [pii]
AID - 10.1385/nmm:8:1-2:107 [doi]
PST - ppublish
SO  - Neuromolecular Med. 2006;8(1-2):107-22. doi: 10.1385/nmm:8:1-2:107.