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Duplication of thePMP22 gene in 17p partial trisomy patients with Charcot-Marie-Tooth type-1A neuropathy

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Abstract

Autosomal dominant Charcot-Marie-Tooth type-1A neuropathy (CMT1A) is a demyelinating peripheral nerve disorder that is commonly associated with a submicroscopic tandem DNA duplication of a 1.5-Mb region of 17p11.2p12 that contains the peripheral myelin genePMP22. Clinical features of CMT1A include progressive distal muscle atrophy and weakness, foot and hand deformities, gait abnormalities, absent reflexes, and the completely penetrant electrophysiologic phenotype of symmetric reductions in motor nerve conduction velocities (NCVs). Molecular and fluorescence in situ hybridization (FISH) analyses were performed to determine the duplication status of thePMP22 gene in four patients with rare cytogenetic duplications of 17p. Neuropathologic features of CMT1A were seen in two of these four patients, in addition to the complex phenotype associated with 17p partial trisomy. Our findings show that the CMT1A phenotype of reduced NCV is specifically associated withPMP22 gene duplication, thus providing further support for thePMP22 gene dosage mechanism for CMT1A.

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Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, TX, USA

    Benjamin B. Roa, Frank Greenberg, Preethi Gunaratne, Lisa G. Shaffer & James R. Lupski

  2. Department of Pediatrics, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, TX, USA

    Frank Greenberg & James R. Lupski

  3. Diagnostic Development Branch, National Center for Human Genome Research, National Institutes of Health, 20892, Bethesda, MD, USA

    Frank Greenberg

  4. Genetics Center, Children's Hospital of Wisconsin, 53226, Milwaukee, WI, USA

    Christine M. Sauer

  5. Department of Pediatrics, Division of Genetics, Medical College of Wisconsin, 53226, Milwaukee, WI, USA

    Mark S. Lubinsky

  6. Department of Pediatrics, Georgetown University Medical Center, 20007, Washington, DC, USA

    Chahira Kozma

  7. Department of Obstetrics and Gynecology, Georgetown, University Medical Center, 20007, Washington, DC, USA

    Jeanne M. Meck

  8. Department of Pediatrics, Oregon Health Sciences University, 97201, Portland, OR, USA

    R. Ellen Magenis

  9. Baylor College of Medicine, Kleberg Cytogenetics Laboratory, 1 Baylor Plaza, 77030, Houston, TX, USA

    Lisa G. Shaffer

  10. Human Genome Center, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, TX, USA

    James R. Lupski

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  1. Benjamin B. Roa
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Roa, B.B., Greenberg, F., Gunaratne, P. et al. Duplication of thePMP22 gene in 17p partial trisomy patients with Charcot-Marie-Tooth type-1A neuropathy. Hum Genet 97, 642–649 (1996). https://doi.org/10.1007/BF02281876

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  • DOI: https://doi.org/10.1007/BF02281876

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