title: Charcot-Marie-Tooth disease: New insights from skin biopsy.
abstract: OBJECTIVE
  To evaluate, by skin biopsy, dermal nerve fibers in 31 patients with 3 common Charcot-Marie-Tooth (CMT) genotypes (CMT1A, late-onset CMT1B, and CMTX1), and rarer forms of CMT caused by mutations in RAB7 (CMT2B), TRPV4 (CMT2C), and GDAP1 (AR-CMT2K) genes.
  
  
  METHODS
  We investigated axonal loss by quantifying Meissner corpuscles and intrapapillary myelinated endings and evaluated morphometric changes in myelinated dermal nerve fibers by measuring fiber caliber, internodal, and nodal gap length.
  
  
  RESULTS
  The density of both Meissner corpuscles and intrapapillary myelinated endings was reduced in skin samples from patients with CMT1A and all the other CMT genotypes. Nodal gaps were larger in all the CMT genotypes though widening was greater in CMT1A. Perhaps an altered communication between axons and glia may be a common feature for multiple forms of CMT. Internodal lengths were shorter in all the CMT genotypes, and patients with CMT1A had the shortest internodes of all our patients. The uniformly shortened internodes in all the CMT genotypes suggest that mutations in both myelin and axon genes may developmentally impede internode formation. The extent of internodal shortening and nodal gap widening are likely both important in determining nerve conduction velocities in CMT.
  
  
  CONCLUSIONS
  This study extends the information gained from skin biopsies on morphologic abnormalities in various forms of CMT and provides insights into potential pathomechanisms of axonal and demyelinating CMT.
authors.affiliation: From the Departments of Neurosciences, Reproductive Sciences, and Odontostomatology (F.M., C.P., L.S.), University Federico II of Naples; Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurological and Movement Sciences, University of Verona (G.M.F.), and the Department of Neurosciences, AOUI Verona (T.C.), University Hospital G.B. Rossi, Verona, Italy; and the Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics, Iowa City.
authors.forename: Fiore
authors.initials: F
authors.lastname: Manganelli
authors.affiliation: From the Departments of Neurosciences, Reproductive Sciences, and Odontostomatology (F.M., C.P., L.S.), University Federico II of Naples; Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurological and Movement Sciences, University of Verona (G.M.F.), and the Department of Neurosciences, AOUI Verona (T.C.), University Hospital G.B. Rossi, Verona, Italy; and the Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics, Iowa City.
authors.forename: Maria
authors.initials: M
authors.lastname: Nolano
authors.affiliation: From the Departments of Neurosciences, Reproductive Sciences, and Odontostomatology (F.M., C.P., L.S.), University Federico II of Naples; Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurological and Movement Sciences, University of Verona (G.M.F.), and the Department of Neurosciences, AOUI Verona (T.C.), University Hospital G.B. Rossi, Verona, Italy; and the Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics, Iowa City.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pisciotta
authors.affiliation: From the Departments of Neurosciences, Reproductive Sciences, and Odontostomatology (F.M., C.P., L.S.), University Federico II of Naples; Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurological and Movement Sciences, University of Verona (G.M.F.), and the Department of Neurosciences, AOUI Verona (T.C.), University Hospital G.B. Rossi, Verona, Italy; and the Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics, Iowa City.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Provitera
authors.affiliation: From the Departments of Neurosciences, Reproductive Sciences, and Odontostomatology (F.M., C.P., L.S.), University Federico II of Naples; Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurological and Movement Sciences, University of Verona (G.M.F.), and the Department of Neurosciences, AOUI Verona (T.C.), University Hospital G.B. Rossi, Verona, Italy; and the Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics, Iowa City.
authors.forename: Gian M
authors.initials: GM
authors.lastname: Fabrizi
authors.affiliation: From the Departments of Neurosciences, Reproductive Sciences, and Odontostomatology (F.M., C.P., L.S.), University Federico II of Naples; Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurological and Movement Sciences, University of Verona (G.M.F.), and the Department of Neurosciences, AOUI Verona (T.C.), University Hospital G.B. Rossi, Verona, Italy; and the Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics, Iowa City.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cavallaro
authors.affiliation: From the Departments of Neurosciences, Reproductive Sciences, and Odontostomatology (F.M., C.P., L.S.), University Federico II of Naples; Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurological and Movement Sciences, University of Verona (G.M.F.), and the Department of Neurosciences, AOUI Verona (T.C.), University Hospital G.B. Rossi, Verona, Italy; and the Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics, Iowa City.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Stancanelli
authors.affiliation: From the Departments of Neurosciences, Reproductive Sciences, and Odontostomatology (F.M., C.P., L.S.), University Federico II of Naples; Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurological and Movement Sciences, University of Verona (G.M.F.), and the Department of Neurosciences, AOUI Verona (T.C.), University Hospital G.B. Rossi, Verona, Italy; and the Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics, Iowa City.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caporaso
authors.affiliation: From the Departments of Neurosciences, Reproductive Sciences, and Odontostomatology (F.M., C.P., L.S.), University Federico II of Naples; Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurological and Movement Sciences, University of Verona (G.M.F.), and the Department of Neurosciences, AOUI Verona (T.C.), University Hospital G.B. Rossi, Verona, Italy; and the Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics, Iowa City.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Shy
authors.affiliation: From the Departments of Neurosciences, Reproductive Sciences, and Odontostomatology (F.M., C.P., L.S.), University Federico II of Naples; Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurological and Movement Sciences, University of Verona (G.M.F.), and the Department of Neurosciences, AOUI Verona (T.C.), University Hospital G.B. Rossi, Verona, Italy; and the Department of Neurology (M.E.S.), University of Iowa Hospitals and Clinics, Iowa City. lusantor@unina.it.
authors.forename: Lucio
authors.initials: L
authors.lastname: Santoro
mesh_terms: D000328:Adult; D001706:Biopsy; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D003711:Demyelinating Diseases / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D012867:Skin / Q000473:pathology*