Aging Symptom Trajectories in Mother Carriers of the FMR1 Premutation

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 (FXPM)。携带FXPM的母亲有将突变基因遗传给孩子的风险，这可能会导致 患有脆性X综合征。FXPM还与显著增加的疾病风险有关，包括 神经退行性疾病，过早绝经，精神疾病，以及执行和社会缺陷。 父母R01试图确定关键FXPM表型(精神健康、执行、社交)的稳定性 FXPM携带者母亲的中年和老年早期与健康对照组的比较(目标1)；调查 与年龄相关症状表达相关的自主神经和分子遗传因素及其相互作用 有育儿压力(目标2)；评估与各年龄段FXPM症状相关的功能限制 (目标3)。我们将通过采用加速纵向设计来跟踪与年龄相关的数据，从而实现这些目标 与75名对照母亲相比，75名FXPM携带者母亲在45-80年间发生了变化。已经过去了- 主要目标是告知与年龄相关的下降的关键年龄段和风险因素，以及奠定 为今后的力学研究奠定基础。这项工作对于制定改进FXPM的策略是必要的 症状，这将改善FXPM携带者母亲及其患有脆性X的孩子的预后 综合症。 这项多样性补充申请将支持有希望的高中学者Ariyo女士获得 在健康相关研究方面的有意义的经验，以激发对科学研究事业的兴趣。

PROJECT SUMMARY/ABSTRACT About 1 in 151 women in the US are carriers of a genetic abnormality called the FMR1 premutation (FXpm). Mothers who carry the FXpm are at risk for passing the mutated gene to their children, which may result in fragile X syndrome. The FXpm is also associated with substantially increased risk for disease, including neurodegenerative disease, premature menopause, psychiatric involvement, and executive and social deficits. The parent R01 seeks to determine the stability of key FXpm phenotypes (mental health, executive, social) across midlife and early old age in FXpm carrier mothers compared to healthy controls (Aim 1); investigate autonomic and molecular-genetic factors associated with age-related symptom expression and their interface with parenting stress (Aim 2); and evaluate functional limitations associated with FXpm symptoms across age (Aim 3). We will accomplish these aims by adopting an accelerated longitudinal design to track age-related change occurring across 45-80 years in 75 FXpm carrier mothers compared to 75 control mothers. The over- arching goal is to inform the critical age periods and risk factors in age-related decline, as well as to lay the groundwork for future mechanistic studies. This work is necessary to develop strategies to ameliorate FXpm symptoms, which will improve outcomes for both FXpm carrier mothers and their children with fragile X syndrome. This diversity supplement application will support Ms. Ariyo, a promising high school scholar, to obtain meaningful experience in health-related research to stimulate interest in research careers in science.