Journal article
Major myelin protein gene (P0) mutation causes a novel form of axonal degeneration
Journal of comparative neurology (1911), Vol.498(2), pp.252-265
09/10/2006
DOI: 10.1002/cne.21051
PMID: 16856127
Abstract
Mutations in the major peripheral nervous system (PNS) myelin protein, myelin protein zero (MPZ), cause Charcot‐Marie‐Tooth Disease type 1B (CMT1B), typically thought of as a demyelinating peripheral neuropathy. Certain MPZ mutations, however, cause adult onset neuropathy with minimal demyelination but pronounced axonal degeneration. Mechanism(s) for this phenotype are unknown. We performed an autopsy of a 73‐year‐old woman with a late‐onset neuropathy caused by an H10P MPZ mutation whose nerve conduction studies suggested severe axonal loss but no demyelination. The autopsy demonstrated axonal loss and reorganization of the molecular architecture of the axolemma. Segmental demyelination was negligible. In addition, we identified focal nerve enlargements containing MPZ and ubiquitin either in the inner myelin intralaminar and/or periaxonal space that separates axons from myelinating Schwann cells. Taken together, these data confirmed that a mutation in MPZ can cause axonal neuropathy, in the absence of segmental demyelination, thus uncoupling the two pathological processes. More important, it also provided potential molecular mechanisms as to how the axonal degeneration occurred: either by disruption of glial–axon interaction by protein aggregates or by alterations in the molecular architecture of internodes and paranodes. This report represents the first study in which the molecular basis of axonal degeneration in the late‐onset CMT1B has been explored in human tissue. J. Comp. Neurol. 498:252–265, 2006. © 2006 Wiley‐Liss, Inc.
Details
- Title: Subtitle
- Major myelin protein gene (P0) mutation causes a novel form of axonal degeneration
- Creators
- Jun LiYunhong BaiEmilia IanakovaMarina GrandisFred UchwatAnna TrostinskaiaKaren M KrajewskiJames GarbernWilliam J KupskyMichael E Shy
- Resource Type
- Journal article
- Publication Details
- Journal of comparative neurology (1911), Vol.498(2), pp.252-265
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company; Hoboken
- DOI
- 10.1002/cne.21051
- PMID
- 16856127
- ISSN
- 0021-9967
- eISSN
- 1096-9861
- Number of pages
- 14
- Grant note
- National Institutes of Health (NIH) (K08 NS048204; NIH R01 NS41319A) Muscular Dystrophy Association
- Language
- English
- Date published
- 09/10/2006
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984018542502771
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