Neuropathic features in fragile X premutation carriers
Neuropathic features in fragile X premutation carriers
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DOI：
10.1002/ajmg.a.31559
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发表时间：
2007-01-01
影响因子：
2
通讯作者：
Hagerman, Paul J.
中科院分区：
文献类型：
--
作者：
Berry-Kravis, Elizabeth;Goetz, Christopher G.;Hagerman, Paul J.
脆性 X 相关震颤/共济失调综合征 (FXTAS) 是一种进行性神经系统疾病，发生在脆性 X 前突变携带者（主要是男性）中，导致中枢神经系统功能障碍，包括震颤、共济失调、帕金森症和认知能力下降。还描述了神经病理性体征。本研究的目的是比较脆性 X 前突变携带者与对照组的神经病变体征，并确定这些体征与 CGG 重复长度和震颤/共济失调的关系。利用神经病变量表来比较来自大量携带者和对照组的受试者的远端腱反射和振动感，这些受试者接受神经系统检查和结构化录像以进行运动障碍评级。男性携带者组在总神经病变、振动和反射评分方面表现出比相应对照组更多的损伤，而女性携带者与对照组没有显着差异。在男性中，校正年龄影响后，CGG 重复长度与总神经病变和反射损伤之间存在相关性。年龄调整的偏相关分析显示，在携带者男性和女性中，神经病变评分与共济失调严重程度之间存在关联，但与震颤无关。这些数据表明，神经病变体征与脆弱的 X 前突变有关，可能是通过与中枢神经系统疾病提出的相同机制发生的，即扩展的 CGG 重复 FMR1 mRNA 的毒性。 (c) 2006 年 Wiley-Liss 公司。
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurological condition occuring in fragile X premutation carriers, predominantly males, and resulting in CNS dysfunction including tremor, ataxia, Parkinsonism, and cognitive decline. Neuropathic signs have also been described. The objective of this study was to compare neuropathic signs in fragile X premutation carriers versus controls and determine the relationship of these signs to CGG repeat length and tremor/ataxia. A neuropathy scale was utilized to compare distal tendon reflexes and vibration sense in subjects from a large cohort of carriers and controls undergoing neurological exam and structured videotaping sessions for movement disorder rating. The male carrier group displayed more impairment on total neuropathy, vibration and reflex scores than the corresponding control group, while female carriers were not significantly different from controls. In males, after correction for age effects, there was a correlation between CGG repeat length and both total neuropathy and reflex impairments. Age-adjusted partial correlation analyses showed an association between neuropathy scores and severity of ataxia but not tremor in carrier males and females. These data suggest that neuropathic signs are associated with the fragile X premutation, presumably occuring through the same mechanism proposed for CNS disease, namely, toxicity from expanded-CGG-repeat FMR1 mRNA. (c) 2006 Wiley-Liss Inc.