PMID- 19447823
OWN - NLM
STAT- MEDLINE
DCOM- 20090909
LR  - 20211020
IS  - 1460-2156 (Electronic)
IS  - 0006-8950 (Print)
IS  - 0006-8950 (Linking)
VI  - 132
IP  - Pt 7
DP  - 2009 Jul
TI  - PMP22 expression in dermal nerve myelin from patients with CMT1A.
PG  - 1734-40
LID - 10.1093/brain/awp113 [doi]
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by a 1.4 Mb duplication on 
      chromosome 17p11.2, which contains the peripheral myelin protein-22 (PMP22) gene. 
      Increased levels of PMP22 in compact myelin of peripheral nerves have been 
      demonstrated and presumed to cause the phenotype of CMT1A. The objective of the 
      present study was to determine whether an extra copy of the PMP22 gene in CMT1A 
      disrupts the normally coordinated expression of PMP22 protein in peripheral nerve 
      myelin and to evaluate PMP22 over-expression in patients with CMT1A and determine 
      whether levels of PMP22 are molecular markers of disease severity. PMP22 
      expression was measured by taking skin biopsies from patients with CMT1A (n = 20) 
      and both healthy controls (n = 7) and patients with Hereditary Neuropathy with 
      liability to Pressure Palsies (HNPP) (n = 6), in which patients have only a 
      single copy of PMP22. Immunological electron microscopy was performed on the skin 
      biopsies to quantify PMP22 expression in compact myelin. Similar biopsies were 
      analysed by real time PCR to measure PMP22 mRNA levels. Results were also 
      correlated with impairment in CMT1A, as measured by the validated CMT Neuropathy 
      Score. Most, but not all patients with CMT1A, had elevated PMP22 levels in myelin 
      compared with the controls. The levels of PMP22 in CMT1A were highly variable, 
      but not in HNPP or the controls. However, there was no correlation between 
      neurological disabilities and the level of over-expression of PMP22 protein or 
      mRNA in patients with CMT1A. The extra copy of PMP22 in CMT1A results in 
      disruption of the tightly regulated expression of PMP22. Thus, variability of 
      PMP22 levels, rather than absolute level of PMP22, may play an important role in 
      the pathogenesis of CMT1A.
FAU - Katona, Istvan
AU  - Katona I
AD  - Department of Neurology, Wayne State University School of Medicine, Detroit, MI 
      48201, USA.
FAU - Wu, Xingyao
AU  - Wu X
FAU - Feely, Shawna M E
AU  - Feely SM
FAU - Sottile, Stephanie
AU  - Sottile S
FAU - Siskind, Carly E
AU  - Siskind CE
FAU - Miller, Lindsey J
AU  - Miller LJ
FAU - Shy, Michael E
AU  - Shy ME
FAU - Li, Jun
AU  - Li J
LA  - eng
GR  - K08 NS048204/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090515
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - 0 (Biomarkers)
RN  - 0 (Myelin Proteins)
RN  - 0 (PMP22 protein, human)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Biomarkers/metabolism
MH  - Charcot-Marie-Tooth Disease/*metabolism/pathology
MH  - Hereditary Sensory and Motor Neuropathy/metabolism
MH  - Humans
MH  - Microscopy, Immunoelectron
MH  - Myelin Proteins/genetics/*metabolism
MH  - Myelin Sheath/*metabolism
MH  - Prospective Studies
MH  - RNA, Messenger/genetics
MH  - Schwann Cells/metabolism
MH  - Severity of Illness Index
MH  - Skin/*metabolism/ultrastructure
PMC - PMC2724915
EDAT- 2009/05/19 09:00
MHDA- 2009/09/10 06:00
PMCR- 2010/07/01
CRDT- 2009/05/19 09:00
PHST- 2009/05/19 09:00 [entrez]
PHST- 2009/05/19 09:00 [pubmed]
PHST- 2009/09/10 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - awp113 [pii]
AID - 10.1093/brain/awp113 [doi]
PST - ppublish
SO  - Brain. 2009 Jul;132(Pt 7):1734-40. doi: 10.1093/brain/awp113. Epub 2009 May 15.