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Peripheral Neuropathy Caused by Proteolipid Protein Gene Mutations
James Y Garbern1, Franca Cambi1, Richard Lewis1
1Department of Neurology, Wayne State University School of Medicine, 4201 St. Antoine Boulevard, 8C UHC, Detroit, Michigan 48201, USACenter for Molecular Medicine and Genetics, Wayne State University School of Medicine, 521 East Canfield, 3216 Scott Hall, Detroit, Michigan 48201, USADepartment of Neurology, Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania 19107, USADepartment of Physical Medicine and Rehabilitation, University of Washington School of Medicine, Seattle, Washington 98195, USADepartment of Neurology, University Hospital, Limoges F-87042, FranceSection of Neurology, Mayo Clinic, Scottsdale, Arizona 85259, USADepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USADepartment of Neurology, University of Washington School of Medicine, Seattle, Washington 98195, USADepartment of Neurosciences, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Abstract:
Pelizaeus-Merzbacher disease (PMD) is a dysmyelinating disorder of the central nervous system typically caused by duplications or missense mutations of the proteolipid protein (PLP) gene. Most investigators have found that peripheral nerve function and structure is normal in PMD patients. We have found that null mutations of the PLP gene cause demyelinating peripheral neuropathy, whereas duplications and a proline 14 to leucine mutation do not affect nerve function. A family with a nonsense mutation at position 144, which affects only PLP but not the alternatively spliced gene product DM20, has a very mild syndrome, including normal peripheral nerve function. Our findings suggest that DM20 alone is sufficient to maintain normal nerve function and that there may be domains of PLP/DM20 that have a relatively more active role in the peripheral nervous system compared with that in the central nervous system.
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