Journal article
Effect of an R69C mutation in the myelin protein zero gene on myelination and ion channel subtypes
Archives of neurology (Chicago), Vol.63(12), pp.1787-1794
2006
DOI: 10.1001/archneur.63.12.1787
PMID: 17172621
Abstract
Background: Most mutations in the myelin protein zero gene (MPZ) typically cause a severe demyelinating/dysmyelinating neuropathy that begins in infancy or an adult-onset axonal neuropathy. Axonal degeneration in the late-onset H10P mutation may be caused by the disruption of axoglial interaction. Objective: To evaluate sural nerve biopsy samples from a patient with early-onset Charcot-Marie-Tooth disease type 1B caused by an arg69-to-cys (R69C) mutation. Design and Participants Biopsies of sural nerves were performed 20 years apart in a patient with an R69C mutation (early onset). In addition, peripheral nerves were obtained from autopsy material from a patient with a T95M mutation (late onset). These nerves were analyzed using light microscopy of semithin sections, teased nerve fiber immunohistochemical analysis, electron microscopy, and immunologic electron microscopy. Main Outcome Measures Pathological changes in sural nerve. Results Both R69C biopsy samples showed prominent demyelination and onion bulb formation, unlike the late-onset T95M mutation, which showed primarily axonal degeneration with no onion bulbs. The sural biopsy sample obtained 20 years earlier from the R69C patient showed minimal difference from the present sample, consistent with the lack of clinical progression during the 2 decades. Teased fiber immunohistochemical analysis of R69C revealed voltage-gated sodium channel subtype 1.8 expressions at the nodes of Ranvier around the areas of segmental demyelination. Internodal length in all R69C nerve fibers was invariably short (>94% of all internodes are <150 μm). Conclusions Morphologic abnormalities in this early-onset R69C neuropathy were severe in childhood but progressed very slowly after adolescence. The switch to voltage-gated sodium channel subtype 1.8 expression at the nodes may provide clues into the pathogenesis of this case of early-onset neuropathy, and the short internodes may contribute to the extremely slowed conduction velocities in this case (<10 m/s).
Details
- Title: Subtitle
- Effect of an R69C mutation in the myelin protein zero gene on myelination and ion channel subtypes
- Creators
- Yunhong Bai - Department of Neurology, Wayne State University School of Medicine, Detroit, Mich, United StatesEmilia IANOKOVA - Department of Neurology, Wayne State University School of Medicine, Detroit, Mich, United StatesJun Li - Department of Neurology, Wayne State University School of Medicine, Detroit, Mich, United StatesQin Pu - Department of Neurology, Wayne State University School of Medicine, Detroit, Mich, United StatesKhaled GHANDOUR - Department of Neurology, Wayne State University School of Medicine, Detroit, Mich, United StatesRock LEVINSON - Department of Physiology and Biophysics, School of Medicine, University of Colorado Health Science Center, Denver, United StatesJean-Jacques MARTIN - Laboratory of Neuropathology, Born-Bunge Institute, and Department of Medicine, University of Antwerp, Antwerp, BelgiumChantal CEUTERICK-DE GROOTE - Laboratory of Neuropathology, Born-Bunge Institute, and Department of Medicine, University of Antwerp, Antwerp, BelgiumRadim MAZANEC - Departments of Adult Neurology and Child Neurology, DNA Laboratory 2nd School of Medicine, Charles University Prague, Prague, Czech RepublicPavel SEEMAN - Departments of Adult Neurology and Child Neurology, DNA Laboratory 2nd School of Medicine, Charles University Prague, Prague, Czech RepublicMichael E SHY - Department of Neurology, Wayne State University School of Medicine, Detroit, Mich, United States
- Resource Type
- Journal article
- Publication Details
- Archives of neurology (Chicago), Vol.63(12), pp.1787-1794
- DOI
- 10.1001/archneur.63.12.1787
- PMID
- 17172621
- NLM abbreviation
- Arch Neurol
- ISSN
- 0003-9942
- eISSN
- 1538-3687
- Publisher
- American Medical Association; Chicago, IL
- Language
- English
- Date published
- 2006
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics
- Record Identifier
- 9984013116602771
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