Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability, affecting as many as 1 in 2500 people. The syndrome is caused by an expansion of a repetitive sequence of nucleotides in the FMR1 gene on the X chromosome, which leads to a dramatic reduction in a protein (FMRP) essential for experience- dependent synaptic development. The proposed project is designed to examine the language development of males with FXS during adolescence and young adulthood, the factors that affect that development, the consequences of language impairments for independent functioning in adulthood, and the specificity of the language profile observed. The project will extend the follow up of an already well-characterized cohort of males with FXS as well recruiting new participants. The project involves an accelerated longitudinal design, with four annual assessments and participants entering between the ages of 15 and 22 years.
Four specific aims will be addressed. (1) The developmental trajectory of important, theoretically motivated, components of language will be described in males with FXS relative to an already characterized typically developing comparison sample of boys of comparable nonverbal mental age. The battery of measures employed will include standardized tests, expressive language samples, and laboratory-based measures. These measures will assess competence in vocabulary, syntax, and pragmatics, as well as atypical language behavior (i.e., perseveration). (2) Potentially important determinants of within-syndrome variation in language development will be investigated. The focus will be on core psychological and behavioral features of FXS (i.e., working memory, autism symptoms, social avoidance, and anxiety), as well as genetic factors (i.e., FMRP expression) and environmental factors (e.g., family emotional climate). (3) The impact of linguistic impairments on adult outcomes reflective of independence participation in the community will be investigated. (4) We will identify those aspects of the language development profile of FXS that are similar (or dissimilar) to idiopathic autism, thereby yielding insights into syndrome specificity and the underlying pathology. This last aim will be addressed by collecting comparable data on a cohort of age- and nonverbal mental age-matched males with idiopathic autism. The primary analytical tool will be hierarchical linear modeling, although other techniques, such as multiple regression, also will be used.

Public Health Relevance

Fragile X syndrome is the leading inherited cause of intellectual disability, affecting as many as 1 in 2,500 people. This project focuses on the development of language in males with the syndrome during adolescence and young adulthood, the factors that affect that development, and the ways in which language impairments limit independent functioning in adulthood. The data collected will increase understanding of the causes, consequences, and possible treatments of FXS.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Urv, Tiina K
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University of California Davis
Schools of Medicine
United States
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Klusek, Jessica; Ruber, Alexis; Roberts, Jane E (2018) Impaired eye contact in the FMR1 premutation is not associated with social anxiety or the broad autism phenotype. Clin Neuropsychol 32:1337-1352
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Klusek, Jessica; Schmidt, Joseph; Fairchild, Amanda J et al. (2017) Altered sensitivity to social gaze in the FMR1 premutation and pragmatic language competence. J Neurodev Disord 9:31
Ashby, Shealyn A; Channell, Marie Moore; Abbeduto, Leonard (2017) Inferential language use by youth with Down syndrome during narration. Res Dev Disabil 71:98-108
Klusek, Jessica; LaFauci, Giuseppe; Adayev, Tatyana et al. (2017) Reduced vagal tone in women with the FMR1 premutation is associated with FMR1 mRNA but not depression or anxiety. J Neurodev Disord 9:16

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