PMID- 17620487
OWN - NLM
STAT- MEDLINE
DCOM- 20070831
LR  - 20131121
IS  - 0003-9942 (Print)
IS  - 0003-9942 (Linking)
VI  - 64
IP  - 7
DP  - 2007 Jul
TI  - Stoichiometric alteration of PMP22 protein determines the phenotype of hereditary 
      neuropathy with liability to pressure palsies.
PG  - 974-8
AB  - BACKGROUND: Hereditary neuropathy with liability to pressure palsies (HNPP) is 
      caused by a 1.4-megabase deletion at chromosome 17p11.2, which bears the PMP22 
      gene and other genes. However, whether other genes besides PMP22 contribute to 
      the phenotype is unknown. Whether any mutation within the coding region of the 
      PMP22 gene ultimately causes HNPP by reducing the amount of peripheral myelin 
      protein 22 (PMP22) expressed in myelin is also unknown. OBJECTIVE: To determine 
      whether affected patients develop a phenotype identical to that found in HNPP and 
      whether the leucine 7 frameshift (Leu7fs) mutation reduces PMP22 levels in 
      myelin. DESIGN: We evaluated affected family members by neurological examination, 
      electrophysiology, and skin biopsies. We identified a large family with a Leu7fs 
      mutation of PMP22 (11 affected members across 3 generations) that predicts 
      truncation of the protein prematurely and eliminates PMP22 expression from the 
      mutant allele. RESULTS: We found that PMP22 levels were reduced in peripheral 
      nerve myelin in dermal skin biopsies in patients with an Leu7fs mutation. Through 
      clinical and electrophysiological evaluation, we also found that patients with 
      the Leu7fs mutation were indistinguishable from patients with HNPP caused by 
      deletion. We also found that a length-dependent axonal loss became pronounced in 
      elderly patients with Leu7fs mutations, similar to what has been described in 
      heterozygous knockout mice (pmp22 +/-). CONCLUSIONS: Taken together, these 
      results confirm that the phenotypic expression is identical in patients with 
      Leu7fs mutation and patients with HNPP caused by chromosome 17p11.2 deletion. 
      They also demonstrate that reduction of PMP22 is sufficient to cause the full 
      HNPP phenotype.
FAU - Li, Jun
AU  - Li J
AD  - Department of Neurology, Wayne State University, 4201 St Antoine St, UHC-8D, 
      Detroit, MI 48201, USA. junli@med.wayne.edu
FAU - Ghandour, Khaled
AU  - Ghandour K
FAU - Radovanovic, Danijela
AU  - Radovanovic D
FAU - Shy, Rosemary R
AU  - Shy RR
FAU - Krajewski, Karen M
AU  - Krajewski KM
FAU - Shy, Michael E
AU  - Shy ME
FAU - Nicholson, Garth A
AU  - Nicholson GA
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
PL  - United States
TA  - Arch Neurol
JT  - Archives of neurology
JID - 0372436
RN  - 0 (Genetic Markers)
RN  - 0 (Myelin Proteins)
RN  - 0 (PMP22 protein, human)
RN  - GMW67QNF9C (Leucine)
SB  - IM
EIN - Arch Neurol. 2007 Oct;64(10):1547. Radovanovic, Danuijola [corrected to 
      Radovanovic, Danijela]
CIN - Arch Neurol. 2007 Jul;64(7):935-6. PMID: 17620482
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Child
MH  - DNA Mutational Analysis
MH  - Down-Regulation/genetics
MH  - Electrodiagnosis
MH  - Female
MH  - *Frameshift Mutation
MH  - Genetic Markers/genetics
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genetic Testing
MH  - Heredodegenerative Disorders, Nervous System/*genetics/metabolism/physiopathology
MH  - Humans
MH  - Leucine/genetics
MH  - Male
MH  - Middle Aged
MH  - Myelin Proteins/biosynthesis/*genetics
MH  - Neural Conduction/genetics
MH  - Peripheral Nerves/*metabolism/pathology/physiopathology
MH  - Peripheral Nervous System Diseases/*genetics/metabolism/physiopathology
MH  - Phenotype
EDAT- 2007/07/11 09:00
MHDA- 2007/09/01 09:00
CRDT- 2007/07/11 09:00
PHST- 2007/07/11 09:00 [pubmed]
PHST- 2007/09/01 09:00 [medline]
PHST- 2007/07/11 09:00 [entrez]
AID - 64/7/974 [pii]
AID - 10.1001/archneur.64.7.974 [doi]
PST - ppublish
SO  - Arch Neurol. 2007 Jul;64(7):974-8. doi: 10.1001/archneur.64.7.974.