Identical point mutations of PMP-22 in Trembler-J mouse and Charcot-Marie-Tooth disease type 1A

Nat Genet. 1992 Dec;2(4):288-91. doi: 10.1038/ng1292-288.


We have investigated the peripheral myelin protein gene, PMP-22, in a family with Charcot-Marie-Tooth disease type 1A (CMT1A). The DNA duplication commonly found in CMT1A was absent in this family, but strong linkage existed between the disease and the CMT1A marker VAW409R3 on chromosome 17p11.2. We found a point mutation in PMP-22 which was completely linked with the disease. The mutation, a proline for leucine substitution in the first putative transmembrane domain, is identical to that recently found in the Trembler-J mouse. The presence of this PMP-22 defect in this CMT1A family and the location of PMP-22 within the DNA duplication associated with CMT1A suggest that both structural alteration and overexpression of PMP-22 may lead to the disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Charcot-Marie-Tooth Disease / classification
  • Charcot-Marie-Tooth Disease / genetics*
  • DNA / genetics
  • Disease Models, Animal
  • Gene Expression
  • Humans
  • Mice
  • Mice, Neurologic Mutants
  • Molecular Sequence Data
  • Multigene Family
  • Myelin Proteins / genetics*
  • Point Mutation


  • Myelin Proteins
  • PMP22 protein, human
  • Pmp22 protein, mouse
  • DNA