Defining the Language Phenotype of the FMR1 Premutation

定义 FMR1 前突变的语言表型

• 批准号: 9891045
• 负责人: Jessica Klusek
• 金额: $ 14.65万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891045
• 关键词: Adult; Advocate; Affect; Award; Biochemical; CGG repeat; Caring; Child; Child Language; Clinical; Cognitive; Control Groups; Data; Development; Disabled Children; Executive Dysfunction; FMR1; Family; Fragile X Syndrome; Friendships; Functional disorder; General Population; Genes; Genetic; Goals; High Prevalence; Impairment; Individual; Intervention; Investigation; Language; Language Disorders; Length; Link; Molecular Abnormality; Mothers; Mutate; National Institute on Deafness and Other Communication Disorders; National Research Service Awards; Nerve Degeneration; Oral; Outcome; Participant; Performance; Phenotype; Population; Prevention; Process; Production; Public Health; Publishing; Quality of life; Research; Risk; Role; Sampling; Semantics; Specificity; Standardization; Techniques; Unemployment; Variant; Woman; Work; autism spectrum disorder; autistic children; clinical effect; clinical phenotype; disorder control; executive function; experience; gene function; improved; indexing; language impairment; literacy; skills; treatment center

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.

项目概要/摘要 尽管 FMR1 前突变是一种常见的基因异常，影响了 1:151 的美国女性， 人们对其临床表型知之甚少。越来越多的研究表明，妈妈们 FMR1 前突变的携带者与语言的语用方面作斗争。但目前还不清楚是否 前突变携带者母亲的口语或书面语言的其他方面也受到损害，因为没有 对这一人群的语言进行系统的调查。了解全方位的语言困难 前突变携带者母亲所经历的问题很重要，因为即使是微妙的语言和读写问题 与教育程度较低、失业、质量较差等负面结果有关 友谊和精神风险。这些负面结果在应用时尤其令人担忧 脆弱 X 家庭的背景，因为它们可能会影响前突变携带者母亲照顾和照顾的能力 为她患有脆性 X 综合症的残疾孩子代言，从而影响了母亲的生活质量 还有她的家人。 该提案代表了对前突变载体语言能力的首次系统研究 妈妈们。我们试图找出区分前突变携带者母亲的口头和书面语言的方面 来自对照母亲和患有自闭症谱系障碍 (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识别前突变语言特征的各个方面 相对于健康人群而言，受到损害。我们还与患有自闭症谱系障碍 (ASD) 儿童的母亲进行了比较，她们 自闭症谱系障碍的遗传倾向增加，并表现出与广泛的自闭症相关的微妙的语言困难 表型。这种跨群体比较方法将告知表型特异性和范围 语言特征可具体追溯到 FMR1 的生化效应。我们也会调查 语言和执行功能障碍之间的相互作用，这是前突变的一个有据可查的方面 表型并被假设影响语言。最后，我们将检查语言之间的关联 和FMR1基因功能。这项研究将加深我们对各种语言表型的理解 与 FMR1 基因功能障碍相关，并将为有针对性的识别/治疗工作的发展提供信息 满足突变前携带者母亲及其家人的具体需求。