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MPZ mutation G123S characterization: evidence for a complex pathogenesis in CMT disease.
Neurology. 2008 Jan 22; 70(4):273-7.Neur

Abstract

OBJECTIVES

To characterize the clinical and cellular phenotypes of a novel MPZ mutation identified in a Chinese family with Charcot-Marie-Tooth (CMT) disease type 1B.

METHODS

The family was evaluated clinically, electrophysiologically, pathologically, and genetically. The wild-type and mutant P(0) fused with fluorescent proteins were expressed in vitro to monitor their intracellular trafficking. Adhesion assay was also performed to evaluate the adhesiveness of cells.

RESULTS

The novel MPZ mutation, c.367G>A, is associated with a late-onset demyelinating CMT phenotype with autosomal dominant inheritance. The median motor nerve conduction velocities of patients in this family ranged from 15.7 to 19.6 m/second. The neuropathologic studies from a sural nerve biopsy revealed a severe loss of myelinated fibers, and some onion bulb formation with clusters of regenerative fibers. Fluorescence analysis demonstrated that the mutant protein was retained ectopically in the endoplasmic reticulum and Golgi apparatus. Adhesion assay demonstrated a defective adhesiveness of cells expressing the mutant P(0)G123S protein.

CONCLUSION

The novel P(0)G123S mutation is associated with typical findings of late-onset demyelinating polyneuropathy in the electrophysiologic and pathologic studies, putatively resulting from aberrant intracellular trafficking of the mutant P(0) protein, which compromises the adhesiveness of the cells.

Authors+Show Affiliations

Section of Neurology, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18209201

Citation

Lee, Y C., et al. "MPZ Mutation G123S Characterization: Evidence for a Complex Pathogenesis in CMT Disease." Neurology, vol. 70, no. 4, 2008, pp. 273-7.
Lee YC, Yu CT, Lin KP, et al. MPZ mutation G123S characterization: evidence for a complex pathogenesis in CMT disease. Neurology. 2008;70(4):273-7.
Lee, Y. C., Yu, C. T., Lin, K. P., Chang, M. H., Hsu, S. L., Liu, Y. F., Lu, Y. C., & Soong, B. W. (2008). MPZ mutation G123S characterization: evidence for a complex pathogenesis in CMT disease. Neurology, 70(4), 273-7. https://doi.org/10.1212/01.wnl.0000296828.66915.bf
Lee YC, et al. MPZ Mutation G123S Characterization: Evidence for a Complex Pathogenesis in CMT Disease. Neurology. 2008 Jan 22;70(4):273-7. PubMed PMID: 18209201.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MPZ mutation G123S characterization: evidence for a complex pathogenesis in CMT disease. AU - Lee,Y C, AU - Yu,C T R, AU - Lin,K P, AU - Chang,M H, AU - Hsu,S L, AU - Liu,Y F, AU - Lu,Y C, AU - Soong,B W, PY - 2008/1/23/pubmed PY - 2008/2/21/medline PY - 2008/1/23/entrez SP - 273 EP - 7 JF - Neurology JO - Neurology VL - 70 IS - 4 N2 - OBJECTIVES: To characterize the clinical and cellular phenotypes of a novel MPZ mutation identified in a Chinese family with Charcot-Marie-Tooth (CMT) disease type 1B. METHODS: The family was evaluated clinically, electrophysiologically, pathologically, and genetically. The wild-type and mutant P(0) fused with fluorescent proteins were expressed in vitro to monitor their intracellular trafficking. Adhesion assay was also performed to evaluate the adhesiveness of cells. RESULTS: The novel MPZ mutation, c.367G>A, is associated with a late-onset demyelinating CMT phenotype with autosomal dominant inheritance. The median motor nerve conduction velocities of patients in this family ranged from 15.7 to 19.6 m/second. The neuropathologic studies from a sural nerve biopsy revealed a severe loss of myelinated fibers, and some onion bulb formation with clusters of regenerative fibers. Fluorescence analysis demonstrated that the mutant protein was retained ectopically in the endoplasmic reticulum and Golgi apparatus. Adhesion assay demonstrated a defective adhesiveness of cells expressing the mutant P(0)G123S protein. CONCLUSION: The novel P(0)G123S mutation is associated with typical findings of late-onset demyelinating polyneuropathy in the electrophysiologic and pathologic studies, putatively resulting from aberrant intracellular trafficking of the mutant P(0) protein, which compromises the adhesiveness of the cells. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/18209201/MPZ_mutation_G123S_characterization:_evidence_for_a_complex_pathogenesis_in_CMT_disease_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=18209201 DB - PRIME DP - Unbound Medicine ER -