Journal article
Mutation of FIG4 causes a rapidly progressive, asymmetric neuronal degeneration
Brain (London, England : 1878), Vol.131(8), pp.1990-2001
08/2008
DOI: 10.1093/brain/awn114
PMCID: PMC2724900
PMID: 18556664
Abstract
Recessive Charcot-Marie-Tooth disease type-4J (CMT4J) and its animal model, the pale tremor mouse (
plt)
, are caused by mutations of the
FIG4
gene encoding a PI(3,5)P
2
5-phosphatase. We describe the 9-year clinical course of CMT4J, including asymmetric, rapidly progressive paralysis, in two siblings. Sensory symptoms were absent despite reduced numbers of sensory axons. Thus, the phenotypic presentation of CMT4J clinically resembles motor neuron disease. Time-lapse imaging of fibroblasts from CMT4J patients demonstrates impaired trafficking of intracellular organelles because of obstruction by vacuoles. Further characterization of
plt
mice identified axonal degeneration in motor and sensory neurons, limited segmental demyelination, lack of TUNEL staining and lack of accumulation of ubiquitinated protein in vacuoles of motor and sensory neurons. This study represents the first documentation of the natural history of CMT4J. Physical obstruction of organelle trafficking by vacuoles is a potential novel cellular mechanism of neurodegeneration.
Details
- Title: Subtitle
- Mutation of FIG4 causes a rapidly progressive, asymmetric neuronal degeneration
- Creators
- Xuebao Zhang - Department of Neurology, Wayne State University, School of Medicine, Detroit, MIClement Y Chow - Department of Neurology, Wayne State University, School of Medicine, Detroit, MIZarife Sahenk - Department of Neurology, Wayne State University, School of Medicine, Detroit, MIMichael E Shy - Department of Neurology, Wayne State University, School of Medicine, Detroit, MIMiriam H Meisler - Department of Neurology, Wayne State University, School of Medicine, Detroit, MIJun Li - Department of Neurology, Wayne State University, School of Medicine, Detroit, MI
- Resource Type
- Journal article
- Publication Details
- Brain (London, England : 1878), Vol.131(8), pp.1990-2001
- Publisher
- Oxford University Press
- DOI
- 10.1093/brain/awn114
- PMID
- 18556664
- PMCID
- PMC2724900
- ISSN
- 0006-8950
- eISSN
- 1460-2156
- Language
- English
- Date published
- 08/2008
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984018700902771
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