PMID- 16476939
OWN - NLM
STAT- MEDLINE
DCOM- 20060505
LR  - 20231213
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 66
IP  - 3
DP  - 2006 Feb 14
TI  - Phenotypic and cellular expression of two novel connexin32 mutations causing 
      CMT1X.
PG  - 396-402
AB  - OBJECTIVE: To determine the phenotypic and cellular expression of two novel 
      connexin32 (Cx32) mutations causing X-linked Charcot-Marie-Tooth disease (CMT1X). 
      METHODS: The authors evaluated several members of two families with CMT1X 
      clinically, electrophysiologically, pathologically, and by genetic testing. The 
      Cx32 mutations were expressed in vitro and studied by immunocytochemistry. 
      RESULTS: In both families, men were more severely affected than women with onset 
      in the second decade of life. In the first family, the phenotype was that of 
      demyelinating polyneuropathy with variable involvement of peripheral nerves. 
      There was clinical evidence of CNS involvement in at least three of the patients, 
      with extensor plantar responses and brisk reflexes. In the second family, the 
      affected man presented with symmetric polyneuropathy and intermediate slowing of 
      conduction velocities, whereas affected women had prominent asymmetric atrophy of 
      the leg muscles. The authors identified two novel missense mutations resulting in 
      L143P amino acid substitution in the first family and in V140E substitution in 
      the second family, both located in the third transmembrane domain of Cx32. 
      Expression of these Cx32 mutations in communication-incompetent HeLa cells and 
      immunocytochemical analysis revealed that both mutants were retained 
      intracellularly and were localized in the Golgi apparatus. In contrast to 
      wild-type protein, they did not form gap junctions. CONCLUSION: These novel 
      connexin32 (Cx32) mutations cause a spectrum of clinical manifestations 
      characteristic of Charcot-Marie-Tooth disease (CMT1X), including demyelinating or 
      intermediate polyneuropathy, which is often asymmetric, and CNS involvement in 
      one family. The position and cellular expression of Cx32 mutations alone cannot 
      fully predict these phenotypic variations in CMT1X.
FAU - Kleopa, K A
AU  - Kleopa KA
AD  - Department of Clinical Neurosciences, The Cyprus Institute of Neurology and 
      Genetics, Nicosia, Cyprus. kleopa@cing.ac.cy
FAU - Zamba-Papanicolaou, E
AU  - Zamba-Papanicolaou E
FAU - Alevra, X
AU  - Alevra X
FAU - Nicolaou, P
AU  - Nicolaou P
FAU - Georgiou, D-M
AU  - Georgiou DM
FAU - Hadjisavvas, A
AU  - Hadjisavvas A
FAU - Kyriakides, T
AU  - Kyriakides T
FAU - Christodoulou, K
AU  - Christodoulou K
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Connexins)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 9DLQ4CIU6V (Proline)
RN  - GMW67QNF9C (Leucine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Aged
MH  - Amino Acid Substitution
MH  - Central Nervous System Diseases/genetics
MH  - Charcot-Marie-Tooth Disease/*genetics/*metabolism/pathology/physiopathology
MH  - Connexins/*genetics/*metabolism
MH  - Demyelinating Diseases/genetics
MH  - Electromyography
MH  - Female
MH  - Glutamic Acid
MH  - HeLa Cells
MH  - Humans
MH  - Leucine
MH  - Male
MH  - Middle Aged
MH  - *Mutation, Missense
MH  - Neural Conduction
MH  - Pedigree
MH  - *Phenotype
MH  - Polyneuropathies/genetics
MH  - Proline
MH  - Sural Nerve/pathology
MH  - Valine
MH  - Gap Junction beta-1 Protein
EDAT- 2006/02/16 09:00
MHDA- 2006/05/06 09:00
CRDT- 2006/02/16 09:00
PHST- 2006/02/16 09:00 [pubmed]
PHST- 2006/05/06 09:00 [medline]
PHST- 2006/02/16 09:00 [entrez]
AID - 66/3/396 [pii]
AID - 10.1212/01.wnl.0000196479.93722.59 [doi]
PST - ppublish
SO  - Neurology. 2006 Feb 14;66(3):396-402. doi: 10.1212/01.wnl.0000196479.93722.59.