MPZ mutation G123S characterization -: Evidence for a complex pathogenesis in CMT disease
MPZ mutation G123S characterization -: Evidence for a complex pathogenesis in CMT disease
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DOI：
10.1212/01.wnl.0000296828.66915.bf
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发表时间：
2008-01-22
期刊：
影响因子：
9.9
通讯作者：
Soong, B. W.
中科院分区：
文献类型：
--
作者：
Lee, Y. C.;Yu, C. T. R.;Soong, B. W.
目的：目的：研究1个腓骨肌萎缩症（CMT）1B型家系中MPZ基因突变的临床和细胞表型特征。方法：对该家系进行临床、电生理、病理和遗传学分析。野生型和突变型P0融合荧光蛋白在体外表达，以监测其细胞内运输。结果：新的MPZ突变株c. 367 G> A与常染色体显性遗传的迟发性脱髓鞘CMT表型相关。该家系患者的运动神经传导速度中位数为15.7 ~ 19.6m/s。腓肠神经活检的神经病理学研究显示，有髓纤维严重缺失，一些再生纤维簇形成洋葱球。荧光分析表明，突变蛋白被异位保留在内质网和高尔基体。结论：新的P（O）G123 S突变与迟发性脱髓鞘性多发性神经病的电生理和病理学表现有关，其发生与突变P（O）蛋白异常胞内转运，损害细胞的粘附性有关。
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 19.6m/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(O)G123S protein.Conclusion: The novel P(O)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(O)protein, which compromises the adhesiveness of the cells.