Birch R C, Hocking D R, Cornish K M, Menant J C, Georgiou-Karistianis N, Godler D E, Wen W, Hackett A, Rogers C, Trollor J N
Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney.
Genes Brain Behav. 2015 Mar;14(3):251-9. doi: 10.1111/gbb.12204. Epub 2015 Mar 25.
Recent evidence suggests that early changes in postural control may be discernible among females with premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene at risk of developing fragile X-associated tremor ataxia syndrome (FXTAS). Cerebellar dysfunction is well described in males and females with FXTAS, yet the interrelationships between cerebellar volume, CGG repeat length, FMR1 messenger RNA (mRNA) levels and changes in postural control remain unknown. This study examined postural sway during standing in a cohort of 22 males with the FMR1 premutation (ages 26-80) and 24 matched controls (ages 26-77). The influence of cerebellar volume, CGG repeat length and FMR1 mRNA levels on postural sway was explored using multiple linear regression. The results provide preliminary evidence that increasing CGG repeat length and decreasing cerebellar volume were associated with greater postural sway among premutation males. The relationship between CGG repeat length and postural sway was mediated by a negative association between CGG repeat size and cerebellar volume. While FMR1 mRNA levels were significantly elevated in the premutation group and correlated with CGG repeat length, FMR1 mRNA levels were not significantly associated with postural sway scores. These findings show for the first time that greater postural sway among males with the FMR1 premutation may reflect CGG repeat-mediated disruption in vulnerable cerebellar circuits implicated in postural control. However, longitudinal studies in larger samples are required to confirm whether the relationships between cerebellar volume, CGG repeat length and postural sway indicate greater risk for neurological decline.
近期证据表明，在有患脆性X相关震颤共济失调综合征（FXTAS）风险的脆性X智力低下1（FMR1）基因前突变扩展（55 - 200个CGG重复序列）的女性中，可能可察觉到姿势控制的早期变化。FXTAS男性和女性患者均有小脑功能障碍的详细描述，但小脑体积、CGG重复长度、FMR1信使核糖核酸（mRNA）水平与姿势控制变化之间的相互关系仍不清楚。本研究在一组22名FMR1前突变男性（年龄26 - 80岁）和24名匹配对照（年龄26 - 77岁）中，检测了站立时的姿势摆动。使用多元线性回归探讨了小脑体积、CGG重复长度和FMR1 mRNA水平对姿势摆动的影响。结果提供了初步证据，表明CGG重复长度增加和小脑体积减小与前突变男性中更大的姿势摆动相关。CGG重复长度与姿势摆动之间的关系是由CGG重复大小与小脑体积之间的负相关介导的。虽然前突变组中FMR1 mRNA水平显著升高且与CGG重复长度相关，但FMR1 mRNA水平与姿势摆动评分无显著关联。这些发现首次表明，FMR1前突变男性中更大的姿势摆动可能反映了CGG重复介导的对参与姿势控制的脆弱小脑回路的破坏。然而，需要在更大样本中进行纵向研究，以确认小脑体积、CGG重复长度与姿势摆动之间的关系是否表明神经功能衰退风险更高。
