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Evidence for a recessive PMP22 point mutation in Charcot–Marie–Tooth disease type 1A

Nature Genetics volume 5, pages 189–194 (1993)Cite this article

Abstract

Charcot–Marie–Tooth disease type 1A (CMT1A) is an autosomal dominant neuropathy that can be caused by dominant point mutations in PMP22 which encodes a peripheral nerve myelin protein. Usually, CMT1A is caused by the duplication of a 1.5–megabase (Mb) region on chromosome 17p11.2–p12 containing PMP22. Deletion of a similar 1.5–Mb region is associated with hereditary neuropathy with liability to pressure palsies (HNPP), a clinically distinct neuropathy. We have identified a severely affected CMT1 patient who is a compound heterozygote for a recessive PMP22 point mutation, and a 1.5 Mb deletion in 17p11.2–p12. A son heterozygous for the PMP22 point mutation had no signs of neuropathy, while two others heterozygous for the deletion had HNPP, suggesting that point mutations in PMP22 can result in dominant and recessive alleles contributing to CMT1A.

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Author information

Authors and Affiliations

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

    Benjamin B. Roa, Liu Pentao, Rocio Ortiz-Lopez, Pragna I. Patel & James R. Lupski

  2. Department of Neurology, Louisiana State University School of Medicine, New Orleans, Louisiana, 70122, USA

    Carlos A. Garcia

  3. Department of Pathology, Louisiana State University School of Medicine, New Orleans, Louisiana, 70122, USA

    Carlos A. Garcia

  4. Department of Neurology, Baylor College of Medicine, Houston, Texas, 77030, USA

    James M. Killian

  5. Department of Molecular Biotechnology, University of Washington, Seattle, Washington, 98195, USA

    Barbara J. Trask

  6. Department of Cell Biology, Swiss Federal Institute of Technology, ETH-Honggerberg, 8093, Zurich, Switzerland

    Ueli Suter

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

    G. Jackson Snipes & Eric M. Shooter

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

    G. Jackson Snipes

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

    Pragna I. Patel & James R. Lupski

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

    James R. Lupski

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Roa, B., Garcia, C., Pentao, L. et al. Evidence for a recessive PMP22 point mutation in Charcot–Marie–Tooth disease type 1A. Nat Genet 5, 189–194 (1993). https://doi.org/10.1038/ng1093-189

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