Fragile X syndrome (FXS) is caused by a mutation in the FMR1 gene on the X chromosome, leading to decreased levels of FMR1 protein (FMRP), which causes the array of neuropsychological impairments that define FXS. Because FXS is an X-linked condition, fewer females display FXS and females with FXS are more mildly affected than males, on average. However, there is a considerable variability in terms of severity of affectedness among females with FXS. The current study was designed to investigate potential genetic (FMRP level and ratio of affected to total chromosomes) and environmental factors (maternal psychological distress and closeness in the mother–child relationship) influencing the cognitive (fluid and crystallized intelligence) and behavioral (anxiety and withdrawal) phenotype of females with FXS. We conducted a prospective 3-year longitudinal study of 16 females with FXS (with up to four assessments, each separated by a year) using an accelerated longitudinal design so that we had coverage of the age range of 10–15 years at study start and 13–18 at study end. We focused on both the level of functioning related to chronological age expectations (standard scores) and absolute change in skill (raw scores) over the 3-year period. At a cross-sectional level, fluid intelligence and crystallized intelligence were both predicted by a closer mother–child relationship and lower maternal psychological distress. However, only fluid intelligence was predicted by a lower ratio of affected to total chromosomes. Anxiety and withdrawal were predicted by a higher ratio of affected to total chromosomes. Withdrawal was also predicted by lower closeness in the mother–child relationship and higher maternal distress. In terms of longitudinal change, gains were observed in fluid and crystallized intelligence, whereas anxious and withdrawn behaviors remained stable over visits. Gains in fluid intelligence were solely predicted by FXS biomarkers (higher FMRP level and lower ratio of affected to total chromosomes), while gains in crystallized intelligence were not predicted by any of the biological and environmental variables. Our results show that FXS biomarkers and maternal variables contribute differentially to the cognitive and behavioral features of the adolescent female with FXS. These findings can help in the design of treatment studies aimed at enhancing cognitive and behavioral abilities in the FXS population.

中文翻译：

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脆性X综合征女性的认知和行为轨迹的遗传和母亲预测因子

易碎X综合征（FXS）是由X染色体上FMR1基因的突变引起的，导致FMR1蛋白（FMRP）的水平降低，这导致了一系列定义FXS的神经心理学障碍。由于FXS是与X连锁的疾病，因此平均而言，显示FXS的女性更少，而患有FXS的女性受到的影响要轻于男性。但是，FXS女性患病严重程度存在很大差异。当前的研究旨在调查影响认知（流体和结晶智能）和行为（焦虑和焦虑）的潜在遗传因素（FMRP水平和受影响的染色体总数之比）和环境因素（孕产妇的心理困扰和亲子关系的亲密性）。退缩）表型与FXS女性。我们使用加速的纵向设计对16名FXS的女性进行了为期3年的前瞻性研究（最多进行四项评估，每项评估之间相隔一年），因此我们在研究开始时覆盖了10-15岁的年龄范围，研究结束时13-18岁。我们专注于在3年内与年龄预期年龄相关的功能水平（标准分数）和技能的绝对变化（原始分数）。从横断面的角度来看，流体智力和结晶智力都是通过亲密的母子关系和较低的孕产妇心理困扰来预测的。但是，只有受影响的染色体与总染色体的比率较低才能预测流体情报。受影响和占总染色体的比例越高，预示着焦虑和退缩。母婴关系中亲密关系的降低和产妇痛苦的增加也预示着退学。在纵向变化方面，观察到流体和结晶智能增加，而焦虑和退缩行为在拜访期间保持稳定。流体智能的获得完全由FXS生物标记物预测（较高的FMRP水平和受影响的染色体与总染色体的比率较低），而结晶智能的获得则不受任何生物学和环境变量的预测。我们的结果表明，FXS生物标志物和母亲变量对FXS青春期女性的认知和行为特征有不同的贡献。这些发现可以帮助设计旨在增强FXS人群的认知和行为能力的治疗研究。