Journal article
Skin biopsies demonstrate MPZ splicing abnormalities in Charcot-Marie-Tooth neuropathy 1B
Neurology, Vol.67(7), pp.1141-1146
2006
DOI: 10.1212/01.wnl.0000238499.37764.b1
PMID: 17030746
Abstract
Objective: To demonstrate that intronic mutations in the myelin protein zero (MPZ) cause Charcot-Marie-Tooth neuropathy 1B (CMT1B) by disrupting MPZ splicing.
Methods: We report a family with a T>G transversion at the invariant + 2 position in intron 4 of MPZ (c.614 + 2T>G) that abolishes 5′ donor site recognition and is predicted to alter MPZ splicing. We obtained detailed clinical and neurophysiologic analysis of the family. We performed skin biopsies to investigate splicing abnormalities, MPZ protein levels, and localization in myelinated nerves.
Results: Patients developed a late onset neuropathy with minimally slow nerve conduction velocities. Skin biopsies confirmed the predicted skipping of exon 4 and downstream frameshift of the mutant MPZ. Quantitative immuno-EM demonstrated normal nerve MPZ levels, suggesting that the mutant MPZ was transported to compact myelin.
Conclusions: Intronic mutations cause CMT1B by disrupting splicing and certain MPZ mutations may cause neuropathy by interacting with the wild type MPZ in the extracellular space of compact myelin.
Details
- Title: Subtitle
- Skin biopsies demonstrate MPZ splicing abnormalities in Charcot-Marie-Tooth neuropathy 1B
- Creators
- A SABET - Department of Neurology, University of Kentucky, Lexington, United StatesJ LI - Department of Neurology, Wayne State University, Detroit, MI, United StatesK GHANDOUR - Department of Neurology, Wayne State University, Detroit, MI, United StatesQ PU - Department of Neurology, Wayne State University, Detroit, MI, United StatesX WU - Department of Neurology, Wayne State University, Detroit, MI, United StatesJ KAMHOLZ - Department of Neurology, Wayne State University, Detroit, MI, United StatesM. E SHY - Department of Neurology, Wayne State University, Detroit, MI, United StatesF CAMBI - Department of Neurology, University of Kentucky, Lexington, United States
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.67(7), pp.1141-1146
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- DOI
- 10.1212/01.wnl.0000238499.37764.b1
- PMID
- 17030746
- ISSN
- 0028-3878
- eISSN
- 1526-632X
- Language
- English
- Date published
- 2006
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984020783102771
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