Defining the Language Phenotype of the FMR1 Premutation

项目总结/摘要 虽然FMR 1前突变是一种常见的遗传异常，在美国影响1：151的女性， 关于其临床表型知之甚少。越来越多的研究表明， FMR 1前突变的携带者与语言的语用方面斗争。然而，目前尚不清楚是否 在前突变携带者的母亲中，口头或书面语言的其他方面也受到损害， 对这一人群的语言进行系统的调查。了解语言的各种困难 突变前携带者母亲经历的是重要的，因为即使是微妙的语言和识字问题， 与教育程度低、失业、质量差等负面结果有关 友谊和精神风险这些负面结果在适用于 脆性X家族的背景，因为它们可能会影响前突变携带者母亲照顾和 倡导她的残疾儿童与脆性X综合征，从而影响生活质量的母亲， 还有她的家人 这一建议代表了第一次系统的调查语言能力的前突变携带者 妈妈们我们试图确定口头和书面语言的方面，区分前突变携带者的母亲 来自对照组母亲和自闭症谱系障碍（ASD）儿童的母亲。我们包含一个控件 一组神经典型的母亲将使我们能够确定突变前语言特征的各个方面， 与健康人群相比，我们还包括与ASD儿童的母亲的比较， 自闭症的遗传易感性增加，并表现出与广泛自闭症相关的微妙的语言困难， 表型。这种交叉群体比较方法将告知表型特异性和 这些语言特征可以特别追溯到FMR 1的生化作用。我们亦会研究 语言和执行功能障碍之间的相互作用，这是一个有据可查的方面， 表型，并假设影响语言。最后，我们将研究语言之间的联系。 FMR 1基因功能这项研究将完善我们对语言表型的全面理解 与FMR 1基因功能障碍有关，并将为针对性的识别/治疗工作的发展提供信息 针对突变前携带者母亲及其家庭的具体需求。

PROJECT SUMMARY/ABSTRACT Although the FMR1 premutation is a common genetic abnormality that affects 1:151 women in the US, relatively little is known about its clinical phenotype. A growing number of studies indicate that mothers who are carriers of the FMR1 premutation struggle with pragmatic aspects of language. However, it is unclear whether other aspects of oral or written language are also impaired in premutation carrier mothers, as there have been no systematic investigations of language in this population. Understanding the full range of language difficulties experienced by premutation carrier mothers is important because even subtle language and literacy problems are linked with negative outcomes such as lower educational attainment, unemployment, poorer quality friendships, and psychiatric risk. These negative outcomes are particularly concerning when applied within the context of fragile X families because they may impact the ability of the premutation carrier mother to care and advocate for her disabled children with fragile X syndrome, thereby impacting quality of life for both the mother as well as her family. This proposal represents the first systematic investigation of language abilities in premutation carrier mothers. We seek to identify aspects of oral and written language that differentiate premutation carrier mothers from control mothers and mothers of children with autism spectrum disorder (ASD). Our inclusion of a control group of neurotypical mothers will allow us to identify aspects of the premutation language profile that are impaired relative to the healthy population. We also include comparison to mothers of children with ASD, who are at increased genetic liability to ASD and show subtle language difficulties associated with the broad autism phenotype. This cross-population comparison approach will inform phenotypic specificity and the range of language features that may be traced specifically to the biochemical effects of FMR1. We will also investigate the interplay between language and executive dysfunction, which is a well-documented aspect of the premutation phenotype and is hypothesized to influence language. Finally, we will examine association between language and FMR1 gene function. This research will refine our understanding of the full range of language phenotypes linked with FMR1 gene dysfunction and will inform the development of identification/treatment efforts targeted towards the specific needs of premutation carrier mothers and their families.