Defining the Language Phenotype of the FMR1 Premutation

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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.