Journal article
Reduced neurofilament expression in cutaneous nerve fibers of patients with CMT2E
Neurology, Vol.85(3), pp.228-234
07/21/2015
DOI: 10.1212/WNL.0000000000001773
PMCID: PMC4516296
PMID: 26109717
Abstract
To investigate the effects of NEFL Glu396Lys mutation on the expression and assembly of neurofilaments (NFs) in cutaneous nerve fibers of patients with Charcot-Marie-Tooth disease type 2E (CMT2E).
A large family with CMT2E underwent clinical, electrophysiologic, and skin biopsy studies. Biopsies were processed by indirect immunofluorescence (IF), electron microscopy (EM), and Western blot analysis.
The clinical features demonstrated intrafamilial phenotypic variability, and the electrophysiologic findings revealed nerve conductions that were either slow or in the intermediate range. All patients had reduced or absent compound muscular action potential amplitudes. Skin biopsies showed axons labeled with the axonal markers protein gene product 9.5 and α-tubulin, but not with NFs. The results of Western blot analysis were consistent with those of IF, showing reduced or absent NFs and normal expression of α-tubulin. EM revealed clusters of regenerated fibers, in absence of myelin sheath abnormalities. Both IF and EM failed to show NF aggregates in dermal axons. The morphometric analysis showed a smaller axonal caliber in patients than in controls. The study of the nodal/paranodal architecture demonstrated that sodium channels and Caspr were correctly localized in patients with CMT2E.
Decrease in NF abundance may be a pathologic marker of CMT2E. The lack of NF aggregates, consistent with prior studies, suggests that they occur proximally leading to subsequent alterations in the axonal cytoskeleton. The small axonal caliber, along with the normal molecular architecture of nodes and paranodes, explain the reduced velocities detected in patients with CMT2E. Our results also demonstrate that skin biopsy can provide evidence of pathologic and pathogenic abnormalities in patients with CMT2E.
Details
- Title: Subtitle
- Reduced neurofilament expression in cutaneous nerve fibers of patients with CMT2E
- Creators
- Chiara Pisciotta - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FL. chiara.pisciotta@gmail.comYunhong Bai - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FLKathryn M Brennan - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FLXingyao Wu - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FLTiffany Grider - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FLShawna Feely - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FLSuola Wang - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FLSteven Moore - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FLCarly Siskind - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FLMichael Gonzalez - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FLStephan Zuchner - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FLMichael E Shy - From the Departments of Neurology (C.P., Y.B., K.M.B., X.W., T.G., S.F., S.W., M.E.S.) and Pathology (S.M.), University of Iowa Hospitals and Clinics, Iowa City; Departments of Neurology (C.S.), Stanford University, CA; Dr. John T. Macdonald Foundation Department of Human Genetics (M.G., S.Z.), University of Miami Miller School of Medicine, FL
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.85(3), pp.228-234
- Publisher
- United States
- DOI
- 10.1212/WNL.0000000000001773
- PMID
- 26109717
- PMCID
- PMC4516296
- ISSN
- 0028-3878
- eISSN
- 1526-632X
- Grant note
- U54 NS053672 / NINDS NIH HHS U54NS065712 / NINDS NIH HHS R01 NS075764 / NINDS NIH HHS U54 NS065712 / NINDS NIH HHS
- Language
- English
- Date published
- 07/21/2015
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984013916002771
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