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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.

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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

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  1. Pragna I. Patel
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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

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

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