The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A

Nat Genet. 1992 Jun;1(3):159-65. doi: 10.1038/ng0692-159.


Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a large DNA duplication on the short arm of human chromosome 17. The trembler (Tr) mouse serves as a model for CMT1A because of phenotypic similarities and because the Tr locus maps to mouse chromosome 11 in a region of conserved synteny with human chromosome 17. Recently, the peripheral myelin gene Pmp-22 was found to carry a point mutation in Tr mice. We have isolated cDNA and genomic clones for human PMP-22. The gene maps to human chromosome 17p11.2-17p12, is expressed at high levels in peripheral nervous tissue and is duplicated, but not disrupted, in CMT1A patients. Thus, we suggest that a gene dosage effect involving PMP-22 is at least partially responsible for the demyelinating neuropathy seen in CMT1A.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Charcot-Marie-Tooth Disease / classification
  • Charcot-Marie-Tooth Disease / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17
  • DNA / genetics
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • Mice, Neurologic Mutants
  • Molecular Sequence Data
  • Multigene Family
  • Myelin Proteins / genetics*
  • Pedigree


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

Associated data

  • GENBANK/M94048