Effect of an R69C mutation in the myelin protein zero gene on myelination and ion channel subtypes
Effect of an R69C mutation in the myelin protein zero gene on myelination and ion channel subtypes
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DOI：
10.1001/archneur.63.12.1787
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发表时间：
2006-12-01
影响因子：
--
通讯作者：
Li, Jun
中科院分区：
文献类型：
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作者：
Bai, Yunhong;Ianokova, Emilia;Li, Jun
背景资料：髓磷脂蛋白零基因（MPZ）中的大多数突变通常会导致婴儿期开始的严重脱髓鞘/髓鞘形成障碍神经病或成人发病的轴突神经病。迟发性H10 P突变的轴突变性可能是由axoglial interaction.Objective：To evaluate腓肠神经活检标本从早发性腓骨肌萎缩症1B型患者引起的arg 69-to-cys（R69 C）mutation.Design and Participants：腓肠神经活检进行了20年除了在一个病人与R69 C突变（早发性）。此外，外周神经从T95 M突变（晚发型）患者的尸检材料中获得。这些神经进行了分析，使用光学显微镜的半薄切片，取笑神经纤维免疫组化分析，电子显微镜，免疫电镜。主要结果措施：腓肠神经的病理变化。结果：两个R69 C活检样本显示突出脱髓鞘和洋葱球的形成，不像迟发性T95 M突变，主要表现为轴突变性，没有洋葱球。20年前从R69 C患者中获得的腓肠活检样本显示与当前样本的差异极小，这与20年间缺乏临床进展一致。R69 C的梳理纤维免疫组织化学分析显示电压门控钠通道亚型1.8在节段性脱髓鞘区域周围的Ranvier结表达。所有R69 C神经纤维的节间长度总是短（> 94%的所有节间< 150 μ m）。结论：在这种早发性R69 C神经病的形态异常是严重的儿童，但在青春期后进展非常缓慢。在淋巴结处转换为电压门控钠通道亚型1.8表达可能为该早发性神经病病例的发病机制提供线索，并且短的节间可能导致该病例中传导速度极慢（< 10 m/s）。
Background: Most mutations in the myelin protein zero gene (MPZ) typically cause a severe demyelinating/dysmyelinating neuropathy that begins in infancy or an adult-onset axonal neuropathy. Axonal degeneration in the late-onset H10P mutation may be caused by the disruption of axoglial interaction.Objective: To evaluate sural nerve biopsy samples from a patient with early-onset Charcot-Marie-Tooth disease type 1B caused by an arg69-to-cys (R69C) mutation.Design and Participants: Biopsies of sural nerves were performed 20 years apart in a patient with an R69C mutation (early onset). In addition, peripheral nerves were obtained from autopsy material from a patient with a T95M mutation ( late onset). These nerves were analyzed using light microscopy of semithin sections, teased nerve fiber immunohistochemical analysis, electron microscopy, and immunologic electron microscopy.Main Outcome Measures: Pathological changes in sural nerve.Results: Both R69C biopsy samples showed prominent demyelination and onion bulb formation, unlike the late-onset T95M mutation, which showed primarily axonal degeneration with no onion bulbs. The sural biopsy sample obtained 20 years earlier from the R69C patient showed minimal difference from the present sample, consistent with the lack of clinical progression during the 2 decades. Teased fiber immunohistochemical analysis of R69C revealed voltage-gated sodium channel subtype 1.8 expressions at the nodes of Ranvier around the areas of segmental demyelination. Internodal length in all R69C nerve fibers was invariably short (> 94% of all internodes are < 150 mu m).Conclusions: Morphologic abnormalities in this early-onset R69C neuropathy were severe in childhood but progressed very slowly after adolescence. The switch to voltage-gated sodium channel subtype 1.8 expression at the nodes may provide clues into the pathogenesis of this case of early-onset neuropathy, and the short internodes may contribute to the extremely slowed conduction velocities in this case (< 10 m/s).