PMID- 9748013
OWN - NLM
STAT- MEDLINE
DCOM- 19981020
LR  - 20190514
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 51
IP  - 3
DP  - 1998 Sep
TI  - A novel PMP22 point mutation causing HNPP phenotype: studies on nerve xenografts.
PG  - 702-7
AB  - BACKGROUND: Hereditary neuropathy with liability to pressure palsies (HNPP) in 
      most cases is caused by a deletion in chromosome 17p11.2-12 or, rarely, mutations 
      resulting in a functional loss of one copy of the peripheral myelin protein 22 
      (PMP22) gene. Point mutations that lie deep within transmembrane (TM) domains 
      causing major structural changes in PMP22 are associated with severe neuropathy. 
      METHODS: A 25-year-old asymptomatic woman with a normal neurologic examination 
      volunteered as a control subject. Electrophysiologic studies showed multiple 
      entrapment neuropathies, prompting a search for a genetic defect. In addition, 
      sural nerve fascicles from the subject were grafted into the cut ends of the 
      sciatic nerve of nude mice and studied at 2, 6, and 8 weeks and compared with 
      controls. RESULTS: Direct sequencing of the PMP22 gene revealed a G-->A 
      transition at position 202 in axon 3 of the PMP22 gene. To determine if this was 
      a causative mutation rather than a polymorphism, 102 DNA samples from controls 
      were studied; none showed a similar base pair change. In the nerve xenografts, 
      there was a marked delay at the onset of myelination and an impairment in the 
      regenerative capacity of the nude mice axons engulfed by the mutant human Schwann 
      cells. The axon tips were enlarged and demonstrated neurofilament density 
      increase. Neurofilament density distribution histograms were bimodal in 
      xenografts as well as in the subject's sural nerve. CONCLUSION: This study 
      provides unequivocal evidence that a base pair change causing a Val30Met 
      substitution at the junction of the first TM domain and the extracellular loop of 
      PMP22 results in the HNPP phenotype.
FAU - Sahenk, Z
AU  - Sahenk Z
AD  - The Ohio State University, Department of Neurology, Neuromuscular Disease Center, 
      Columbus 43210, USA.
FAU - Chen, L
AU  - Chen L
FAU - Freimer, M
AU  - Freimer M
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 (Myelin Proteins)
RN  - 0 (Neurofilament Proteins)
RN  - 0 (PMP22 protein, human)
RN  - 0 (Pmp22 protein, mouse)
SB  - IM
CIN - Neurology. 1998 Sep;51(3):664-5. PMID: 9748005
MH  - Adult
MH  - Animals
MH  - Charcot-Marie-Tooth Disease/*genetics/physiopathology
MH  - Chromosomes, Human, Pair 17
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Microscopy, Electron
MH  - Myelin Proteins/*genetics
MH  - Neurofilament Proteins/ultrastructure
MH  - Paresis/*genetics/physiopathology
MH  - Pedigree
MH  - Point Mutation
MH  - Polymorphism, Single-Stranded Conformational
MH  - Pressure/adverse effects
MH  - Sural Nerve/pathology/transplantation/ultrastructure
MH  - Transplantation, Heterologous
EDAT- 1998/09/25 00:00
MHDA- 1998/09/25 00:01
CRDT- 1998/09/25 00:00
PHST- 1998/09/25 00:00 [pubmed]
PHST- 1998/09/25 00:01 [medline]
PHST- 1998/09/25 00:00 [entrez]
AID - 10.1212/wnl.51.3.702 [doi]
PST - ppublish
SO  - Neurology. 1998 Sep;51(3):702-7. doi: 10.1212/wnl.51.3.702.