Brain, Vol. 123, No. 2, 222-233,
February 2000
© 2000 Oxford University Press
Charcot–Marie–Tooth disease type 1
Molecular pathogenesis to gene therapy
1 Department of Neurology, 2 Center for Molecular Medicine and Genetics and 3 Department of Biological Sciences, Wayne State University School of Medicine, Detroit, 4 Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA and 5 Department of Neurology, Ospedale Maggiore-Policlinico, Milan, Italy
Correspondence to:
John Kamholz, MD, Department of Neurology, Wayne State University School of Medicine, Elliman Building, Room 3301, 421 E. Canfield, Detroit, MI 48201, USA E-mail: j_kamholz{at}wayne.edu
Charcot–Marie–Tooth disease type 1 (CMT1) is caused by mutations in the peripheral myelin protein, 22 kDa (PMP22) gene, protein zero (P0) gene, early growth response gene 2 (EGR-2) and connexin-32 gene, which are expressed in Schwann cells, the myelinating cells of the peripheral nervous system. Although the clinical and pathological phenotypes of the various forms of CMT1 are similar, including distal muscle weakness and sensory loss, their molecular pathogenesis is likely to be quite distinct. In addition, while demyelination is the hallmark of CMT1, the clinical signs and symptoms of the disease are probably produced by axonal degeneration, not demyelination itself. In this review we discuss the molecular pathogenesis of CMT1, as well as approaches to an effective gene therapy for this disease.
CMT; myelination; Schwann cell axonal interactions; gene therapy
AVR = adenoviral vectors; BiP/GRP78 = growth related protein, 78 kDa; CMT = Charcot–Marie–Tooth disease; EGR-2 = early growth response gene 2; MAG = myelin associated glycoprotein; MBP = myelin basic protein; PMP22 = peripheral myelin protein (22 kDa); P0 = protein zero
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