FMR1 CGG repeat length predicts motor dysfunction in premutation carriers
FMR1 CGG repeat length predicts motor dysfunction in premutation carriers
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DOI：
10.1212/01.wnl.0000281692.98200.f5
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发表时间：
2008-04-15
期刊：
影响因子：
9.9
通讯作者：
Hagerman, P. J.
中科院分区：
文献类型：
--
作者：
Leehey, M. A.;Berry-Kravis, E.;Hagerman, P. J.
背景资料：脆性X相关性震颤/共济失调综合征（FXTAS）是一种新近发现的老年脆性X智力低下1（FMR 1）前突变携带者（尤其是男性）的神经退行性疾病。核心运动特征是动作震颤、步态共济失调和帕金森症。携带者的CGG重复序列扩增（55到200）;更大的扩增导致脆性X综合征，这是智力迟钝和自闭症最常见的遗传原因。本研究确定CGG重复序列长度是否与前突变携带者运动功能障碍的严重程度和类型相关。方法：对年龄>= 50岁、有脆性X综合征家族史的患者进行结构化录像。运动障碍的神经学家，不知道携带者的状况，用修改后的标准化评定量表对磁带进行评分。CGG重复序列长度分析纳入妇女的激活率，这措施的百分比正常的活跃染色体X alleles.Results：男性载体（n = 54）有显着较差的总运动评分，特别是在震颤和共济失调，比年龄匹配的男性noncarriers（n = 51）。女性携带者（n = 82）和非携带者（n = 39）之间存在差异的趋势。在男性中，CGG重复增加与所有运动体征的更大损伤相关。在妇女中，当激活率被认为是，增加CGG与更大的ataxia.Conclusions相关：CGG重复序列的大小是显着相关的整体运动障碍的前突变携带者。尽管这种关联在男性中最为明显，并涵盖了整体运动障碍--震颤、共济失调和帕金森症--但这种关联存在于女性携带者中的共济失调。这是首次报道女性脆性X相关震颤/共济失调综合征的前突变状态与运动特征之间存在显着相关性。
Background: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently described, under-recognized neurodegenerative disorder of aging fragile X mental retardation 1 (FMR1) premutation carriers, particularly men. Core motor features are action tremor, gait ataxia, and parkinsonism. Carriers have expanded CGG repeats (55 to 200); larger expansions cause fragile X syndrome, the most common heritable cause of mental retardation and autism. This study determines whether CGG repeat length correlates with severity and type of motor dysfunction in premutation carriers.Methods: Persons aged >= 50 years with a family history of fragile X syndrome underwent structured videotaping. Movement disorder neurologists, blinded to carrier status, scored the tapes using modified standardized rating scales. CGG repeat length analyses for women incorporated the activation ratio, which measures the percentage of normal active chromosome X alleles.Results: Male carriers (n = 54) had significantly worse total motor scores, especially in tremor and ataxia, than age-matched male noncarriers (n = 51). There was a trend toward a difference between women carriers (n = 82) and noncarriers (n = 39). In men, increasing CGG repeat correlated with greater impairment in all motor signs. In women, when activation ratio was considered, increasing CGG correlated with greater ataxia.Conclusions: CGG repeat size is significantly associated with overall motor impairment in premutation carriers. Whereas this association is most pronounced for men and covers overall motor impairment-tremor, ataxia, and parkinsonism-the association exists for ataxia among women carriers. This is the first report of a significant correlation between the premutation status and a motor feature of fragile X-associated tremor/ataxia syndrome in women.