Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

Nature Genetics volume 1, pages 159–165 (1992)Cite this article

Abstract

Charcot–Marie-–ooth 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 PM–22P. 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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

References

  1. Charcot, J.-M. & Marie, P. Rev. Med. 6, 97–138 (1886).

    Google Scholar 

  2. Lupski, J.R. et al. in Current Neurology, (ed. Appel, S.) 1–25 ( Mosby-Yearbook, Chicago, 1991).

    Google Scholar 

  3. Lupski, J.R. et al. Cell 66, 219–232 (1991).

    Article  CAS  PubMed  Google Scholar 

  4. Skre, H. Clin. Genet. 6, 98–118 (1974).

    Article  CAS  PubMed  Google Scholar 

  5. Lupski, J. R. et al. Nature Genet. 1, 29–33 (1992).

    Article  CAS  PubMed  Google Scholar 

  6. Raeymaekers, P. et al. Neuromuscular Disorders 1, 93–97 (1991).

    Article  CAS  PubMed  Google Scholar 

  7. Raeymaekers, P. et al. J. med. Genet 29, 5–11 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hoogendijk, J.E. et al. Hum. Genet. 88, 215–218 (1991).

    Article  CAS  PubMed  Google Scholar 

  9. Falconer, D.S. J. Genet. 50, 192–201 (1951).

    Article  CAS  PubMed  Google Scholar 

  10. Henry, E.W., Cowen, J.S. & Sidman, R.L., J. neuropathol. exp. Neurol. 42, 688–706 (1983).

    Article  CAS  PubMed  Google Scholar 

  11. Davisson, M.T. & Roderick, T.H. Cytogenet. cell Genet. 22, 552–564 (1977).

    Article  Google Scholar 

  12. Buchberg, A.M., Brownell, E., Nagata, S., Jenkins, N.A. & Copeland, N.G. Genetics 122, 153–161 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Buchberg, A.M., Moskow, J.J., Buckwalter, M.S. & Camper, S.A., Mammal. Genome 1, 5158–5191 (1991).

    Article  Google Scholar 

  14. Suter, U. et al. Nature 356, 241–244 (1992).

    Article  CAS  PubMed  Google Scholar 

  15. Suter, U. et al. Proc. natn. Acad. Sci. U.S.A. 89, 4382–4386 (1992).

    Article  CAS  Google Scholar 

  16. Snipes, G.J., Suter, U., Welcher, A.A. & Shooter, E.M. J. cell. Biol. 117, 225–238 (1992).

    Article  CAS  PubMed  Google Scholar 

  17. Henry, E.W. & Sidman, R.L., 241, 344–346 (1988).

  18. Perkins, C.S., Aguayo, A.J. & Bray, G.M., Neuropathol. App. Neurobiol. 7, 115–126 (1981).

    Article  CAS  Google Scholar 

  19. Kitamura, K., Sakamoto, Y., Suzuki, M. & Uyemura, K. . in Proceedings of the 6th International Symposium on Glycoconjugates (eds Yamaka, T., Osawa, T., Handa, S.) 273–274 (Japan Scientific Societies Press, Tokyo, 1981).

    Google Scholar 

  20. Manfioletti, G., Ruaro, M.E., Del Sal, G., Philipson, L. & Schneider, C., Molec. cell Biol. 10, 2924–2930 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Welcher, A.A., Suter, U., De Leon, M., Snipes, G.J. & Shooter, E.M., Proc. natn. Acad. Sci. U.S.A. 88, 7195–7199 (1991).

    Article  CAS  Google Scholar 

  22. Guzzetta, V. et al. Genomics (in the press).

  23. Low, P.A. Neuropathol. App. Neurobiol. 3, 81–92 (1977).

    Article  Google Scholar 

  24. Low, P.A. & McLeod, J.G. J. neurol. Sci. 26, 565–574 (1975).

    Article  CAS  PubMed  Google Scholar 

  25. Low, P.A. J. neurol. Sci. 30, 327–341 (1976).

    Article  CAS  PubMed  Google Scholar 

  26. Low, P.A. J. neurol. Sci. 30, 343–368 (1976).

    Article  CAS  PubMed  Google Scholar 

  27. Dyck, P.J. in Peripheral Neuropathy (edsDyck, Thomas, Lambert & Bunge)1600–1655 (Saunders, Philadelphia, 1984).

    Google Scholar 

  28. Aguayo, A.J. et al. Nature 265, 73–75 (1977).

    Article  CAS  PubMed  Google Scholar 

  29. Nukada, H., Dyck, P.J. & Karnes, J.L. Ann. Neurol. 14, 648–655 (1983).

    Article  CAS  PubMed  Google Scholar 

  30. Nukada, H. & Dyck, P.J., Ann. Neurol. 16, 238–241 (1984).

    Article  CAS  PubMed  Google Scholar 

  31. deWaegh, S.M., Lee, V.M.-Y., & Brady, S.T. Cell 68, 451–463 (1992).

    Article  CAS  Google Scholar 

  32. De Leon, M., Welcher, A.A., Suter, U. & Shooter, E.M. J. neurosci. Res. 26, 437–448 (1991).

    Article  Google Scholar 

  33. Spreyer, P. et al. EMBO J. 10, 3661–3668 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Morgan, L., Jessen, K.R. & Mirsky, R.J. cell Biol. 112, 457–467 (1991).

    Article  CAS  Google Scholar 

  35. Francke, U., Yang-Feng, T.L., Brissenden, J.E. & Ullrich, A. CSH Symp. Quant. Biol. 51, 855–866 (1986).

    Article  CAS  Google Scholar 

  36. Francke, U. & Busby, N., Cytogenet. cell Genet. 14, 313–319 (1975).

    Article  CAS  PubMed  Google Scholar 

  37. VanTuinen, P., Rich, D.C., Summers, K.M. & Ledbetter, D.H., Genomics 1, 374–381 (1987).

    Article  CAS  Google Scholar 

  38. Greenberg, F. et al. Am. J. hum. Genet. 49, 1207–1218 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Elder, F.F.B., Nichols, M.M., Hood, O.J. & Harrison, W.R. Am. J. med. Genet. 20, 519–524 (1985).

    Article  CAS  PubMed  Google Scholar 

  40. Chirgwin, J.M., Przybyla, A.E., MacDonald, R.J. & Rutter, W.J., Biochem. 18, 5294–5299 (1979).

    Article  CAS  Google Scholar 

  41. Chomczynski, P. & Sacchi, N.,Anal.Biochem 162, 156–159 (1987).

    Article  CAS  PubMed  Google Scholar 

  42. Fuqua, S.A.W., Fitzgerald, S.D. & McGuire, W.L.,BioTechniques 9, 206–211 (1990).

    CAS  PubMed  Google Scholar 

  43. Evans, G.A., Lewis, K. & Rothernberg, B.E., Gene 79, 9–20 (1989).

    Article  CAS  PubMed  Google Scholar 

  44. Patel, P.I. et al. Am. J. hum. Genet. 47, 926–934 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Wright, E.C., Goldgar, D.E., Fain, P.R., Barker, D.F. & Skolnick, M.H. Genomics 7, 103–109 (1990).

    Article  CAS  PubMed  Google Scholar 

  46. Trask, B.J., Massa, H., Kenwrick, S. & Gitschier, J., Am. J. hum. Genet. 48, 1–15 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA

    Pragna I. Patel, Benjamin B. Roa, Raymond Schoener-Scott, Liu Pentao & James R. Lupski

  2. Human Genome Center, Baylor College of Medicine, Houston, Texas, 77030, USA

    Pragna I. Patel & James R. Lupski

  3. Amgen Inc., Amgen Center, Thousand Oaks, California, 91320, USA

    Andrew A. Welcher

  4. Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305, USA

    Andrew A. Welcher, G. Jackson Snipes, Eric M. Shooter & Ueli Suter

  5. Biomedical Sciences Division, Lawrence Livermore National Laboratory, Livermore, California, 94550, USA

    Barbara J. Trask

  6. Department of Neuropathology, Stanford University School of Medicine, Stanford, California, 94305, USA

    G. Jackson Snipes

  7. Departments of Neurology and Pathology, Louisiana State University, New Orleans, Louisiana, 70112, USA

    Carlos A. Garcia

  8. Department of Genetics and Pediatrics, Stanford University School of Medicine, Stanford, California, 94305, USA

    Uta Francke

  9. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, 94305, USA

    Uta Francke

  10. Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77030, USA

    James R. Lupski

Authors
  1. Pragna I. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Benjamin B. Roa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew A. Welcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raymond Schoener-Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Barbara J. Trask
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Liu Pentao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Jackson Snipes
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Carlos A. Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Uta Francke
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eric M. Shooter
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. James R. Lupski
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ueli Suter
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Patel, P., Roa, B., Welcher, A. et al. The gene for the peripheral myelin protein PMP–22 is a candidate for Charcot–Marie–Tooth disease type 1A. Nat Genet 1, 159–165 (1992). https://doi.org/10.1038/ng0692-159

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0692-159

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing