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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 P0 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 P0G123S protein.
Conclusion: The novel P0G123S 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 P0 protein, which compromises the adhesiveness of the cells.
Glossary
- AI=
- aggregation index;
- cDNA=
- complementary DNA;
- CMT=
- Charcot–Marie–Tooth;
- DAPI=
- 4′-6-diamidino-2-phenylindole;
- ER=
- endoplasmic reticulum;
- NCV=
- nerve conduction velocity.
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