BACKGROUND Individuals with premutation alleles of the fragile X mental retardation 1 (FMR1) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in FMR1 premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS. METHODS We examined postural stability in 18 premutation carriers ages 46-77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG repeat length was measured for each premutation carrier, and MRI and neurological evaluations were conducted to identify carriers who currently met criteria for FXTAS. Of the 18 premutation carriers, seven met criteria for definite/probable FXTAS (FXTAS+), seven showed no MRI or neurological signs of FXTAS (FXTAS-), and four were inconclusive due to insufficient data. RESULTS Compared to controls, premutation carriers showed increased center of pressure (COP) variability in the mediolateral (COPML) direction during static stance and reduced COP variability in the anterior-posterior (COPAP) direction during dynamic AP sway. They also showed reductions in COPML complexity during each postural condition. FXTAS+ individuals showed reduced COPAP variability compared to FXTAS- carriers and healthy controls during dynamic AP sway. Across all carriers, increased sway variability during static stance and decreased sway variability in target directions during dynamic sways were associated with greater CGG repeat length and more severe neurologically rated posture and gait abnormalities. CONCLUSION Our findings indicate that aging FMR1 premutation carriers show static and dynamic postural control deficits relative to healthy controls implicating degenerative processes of spinocerebellar and cerebellar-brainstem circuits that may be independent of or precede the onset of FXTAS. Our finding that FXTAS+ and FXTAS- premutation carriers differed on their level of intentional AP sway suggests that neural mechanisms of dynamic postural control may be differentially impacted in patients with FXTAS, and its measurement may be useful for rapidly and precisely identifying disease presence and onset.

中文翻译：

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衰老的脆弱X智力低下1（FMR1）基因预突变载体的静态和动态姿势控制缺陷。

背景技术具有易碎X智力低下1（FMR1）基因的突变前等位基因的个体在衰老过程中有发展为易碎X相关震颤/共济失调综合征（FXTAS）的风险。需要确定与FMR1突变前体的衰老相关的运动问题，以确定神经退行性过程并建立新的生物行为指标，以帮助识别罹患FXTAS的最大风险的个体。方法我们检查了18位年龄在46-77岁的突变前携带者和14位年龄匹配的健康对照者的姿势稳定性。参加者在一个受力平台上完成了静态姿势测试和两项动态姿势摇摆测试，以量化姿势的变异性和复杂性。测量每个预突变载体的CGG重复长度，进行了MRI和神经病学评估，以识别当前符合FXTAS标准的携带者。在18个突变载体中，有7个满足确定/可能的FXTAS（FXTAS +）的标准，其中7个没有显示MRI或FXTAS的神经系统症状（FXTAS-），还有4个由于数据不足而没有定论。结果与对照相比，变异子携带者在静止姿势期间在中外侧（COPML）方向上表现出压力中心（COP）变异性增加，而在动态AP摇摆过程中在前后（COPAP）方向上表现出较低的COP变异性。他们还表明，在每种姿势状态下，COPML的复杂性均降低了。与FXTAS携带者和健康对照在动态AP摇摆期间相比，FXTAS +个体显示出降低的COPAP变异性。在所有运营商中，静态姿势时摇摆变化增加，动态摇摆时目标方向摇摆变化减小，这与更大的CGG重复长度和更严重的神经学上的姿势和步态异常有关。结论我们的发现表明，相对于健康对照，衰老的FMR1突变前体携带者存在静态和动态的姿势控制缺陷，这牵涉到脊髓小脑和小脑-脑干电路的退化过程，而这些过程可能与FXTAS无关或在FXTAS发作之前发生。我们的发现FXTAS +和FXTAS-突变载体在其有意AP摇摆的水平上有所不同，这表明动态姿势控制的神经机制在FXTAS患者中可能受到不同的影响，其测量结果可能有助于快速，准确地识别疾病的存在和发作。