PMID- 10489052
OWN - NLM
STAT- MEDLINE
DCOM- 19991029
LR  - 20220129
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 53
IP  - 4
DP  - 1999 Sep 11
TI  - Myelin uncompaction in Charcot-Marie-Tooth neuropathy type 1A with a point
      mutation of peripheral myelin protein-22.
PG  - 846-51
AB  - BACKGROUND: The peripheral myelin protein-22 (PMP22) gene has four transmembrane 
      domains, two extracellular loops, and a short cytoplasmic tail. Its roles in the 
      peripheral nervous system remain unclear. The most common cause of
      Charcot-Marie-Tooth neuropathy type 1A (CMT1A) is a PMP22 gene duplication.
      Missense point mutations in the transmembrane domains are rare alternative causes
      that have undetermined pathogenetic mechanisms. OBJECTIVE: To investigate the
      phenotype-to-genotype correlations in a pedigree with unusual CMT1A. METHODS: We 
      identified a pedigree with an autosomal dominant motor-sensory neuropathy and
      severely reduced nerve conduction velocities who did not have the PMP22
      duplication. Specimens from sural nerve biopsies from two patients of different
      ages were evaluated morphometrically. By automated direct nucleotide sequencing
      we analyzed PMP22 and the gene of the major structural myelin protein zero (P0). 
      RESULTS: Nucleotide 159 of PMP22 showed an A-to-T heterozygous mutation,
      predicted to cause an aspartate-to-valine substitution at codon 37 in the first
      extracellular loop of the protein. The mutation co-segregated with the disease in
      the pedigree and was absent in 80 healthy controls. The histopathologic phenotype
      was a de-remyelinating neuropathy with onion bulb formations, characterized by
      prominent uncompaction of the myelin sheath in the majority of fibers and by
      frequent tomacula. CONCLUSION: We have described a novel mutation in the first
      extracellular loop of PMP22 associated with an atypical CMT1A that overlaps
      pathologically with CMT1B caused by point mutations in the extracellular domain
      of P0.
FAU - Fabrizi, G M
AU  - Fabrizi GM
AD  - Department of Neurological and Visual Sciences, University of Verona, Italy.
FAU - Cavallaro, T
AU  - Cavallaro T
FAU - Taioli, F
AU  - Taioli F
FAU - Orrico, D
AU  - Orrico D
FAU - Morbin, M
AU  - Morbin M
FAU - Simonati, A
AU  - Simonati A
FAU - Rizzuto, N
AU  - Rizzuto N
LA  - eng
GR  - 1089/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Myelin Proteins)
RN  - 0 (PMP22 protein, human)
SB  - IM
MH  - Adult
MH  - Charcot-Marie-Tooth Disease/*genetics
MH  - Child
MH  - Female
MH  - Humans
MH  - Male
MH  - Microscopy, Electron
MH  - Middle Aged
MH  - Myelin Proteins/*genetics
MH  - Myelin Sheath/ultrastructure
MH  - Pedigree
MH  - Point Mutation/*genetics
EDAT- 1999/09/17 00:00
MHDA- 1999/09/17 00:01
CRDT- 1999/09/17 00:00
PHST- 1999/09/17 00:00 [pubmed]
PHST- 1999/09/17 00:01 [medline]
PHST- 1999/09/17 00:00 [entrez]
AID - 10.1212/wnl.53.4.846 [doi]
PST - ppublish
SO  - Neurology. 1999 Sep 11;53(4):846-51. doi: 10.1212/wnl.53.4.846.