Aging Language Trajectories in Premutation Carrier Mothers

项目摘要/摘要 在美国，大约每151名女性中就有一名携带一种名为FMR1前突变的基因异常。 携带FMR1前突变的母亲有将突变基因遗传给孩子的风险，这可能 导致脆性X综合征。FMR1前突变也与其自身的临床症状有关， 似乎随着年龄的增长而恶化。新出现的证据表明，前突变携带者母亲可能 经历与年龄相关的语言表达技能过早下降，最早可能在第三个或第三个月开始 生命的第四个十年。语言产出缺陷阻碍有效沟通，降低人们对 能力，并对社会互动产生负面影响。前突变携带者母亲特别容易患上 语言缺陷的负面后果，因为他们是脆弱儿童的主要照顾者 X和有效的沟通能力对于照顾和倡导他们的残疾儿童是必要的。然而，一位少校 这一领域的障碍是，所有现有的证据都是从横断面数据中收集的。纵向 需要研究来证实在成年早期到中期是否存在与年龄相关的语言衰退。 还有必要更好地了解环境因素，如增加的育儿压力 与照顾残疾儿童相关，有助于前突变症状的表现 时间到了。对衰老前突变表型及其机制的了解不足代表了大量的 预突变携带者的有效临床管理的障碍，因为我们缺乏了解 随着时间的推移，这种基因异常的长期影响。 这项研究将是对前突变携带者的第一次纵向调查。我们会 描述与年龄相关的语言技能在成年早期到中期的变化(目标1)，并确定 增加的育儿压力对衰老轨迹的影响(目标2)。我们正以独特的姿态继续这项工作 鉴于我们获得了一个罕见的语料库，这些语料库之前收集了来自前突变的纵向语言样本 携带者母亲。我们将使用成熟的语言样本分析技术来提取新的语言 这些现有样本的变量：命题密度、语法复杂性和不流利性。领养 一种创新的统计方法-加速纵向设计-我们将跟踪与年龄相关的变化 这些特征贯穿于成年早期到中期(30-62岁)。这项工作将对当前 了解衰老前突变表型，告知干预的关键年龄阶段，并阐明 将育儿压力作为改善突变前症状的潜在干预目标。

PROJECT SUMMARY/ABSTRACT About 1 in 151 women in the US are carriers of a genetic abnormality called the FMR1 premutation. Mothers who carry the FMR1 premutation are at risk for passing the mutated gene to their children, which may result in fragile X syndrome. The FMR1 premutation is also associated with its own clinical symptoms, which appear to worsen with age. New, emerging evidence suggests that premutation carrier mothers may experience premature age-related decline in language production skills that may begin as early as the third or fourth decade of life. Language production deficits impede effective communication, reduce perceptions of competence, and negatively impact social interaction. Premutation carrier mothers are particularly vulnerable to the negative consequences of language deficits, as they are the primary caregivers for their children with fragile X and effective communication skills are necessary to care and advocate for their disabled children. Yet, a major obstacle in the field is that all existing evidence has been gleaned from cross-sectional data. Longitudinal research is needed to confirm the presence of age-related linguistic decline across early-to-middle adulthood. There is also a need to better understand how environmental factors, such as elevated parenting stress associated with caring for a child with a disability, contribute to the expression of premutation symptoms over time. Poor understanding of the aging premutation phenotype and its mechanisms represents a substantial barrier to effective clinical management of premutation carriers, as we lack the data needed to understand the long-term effects of this genetic abnormality over time. The present study will represent one of the first longitudinal investigations of premutation carriers. We will delineate age-related changes in language skills across early-to-mid adulthood (Aim 1) and determine the effect of elevated parenting stress on aging trajectories (Aim 2). We are uniquely poised to pursue this work given our access to a rare corpus of previously-collected longitudinal language samples from premutation carrier mothers. We will use well-established language sample analytic techniques to extract new language variables from these existing samples: propositional density, grammatical complexity, and dysfluency. Adopting an innovative statistical approach—an accelerated longitudinal design-- we will track age-related change in these features across early-to-mid adulthood (30-62 years). This work will contribute significantly to current understanding of the aging premutation phenotype, inform critical age periods for intervention, and shed light on parenting stress as a potential intervention target for ameliorating premutation symptoms.