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Brown W.T.,Institute for Basic Research in Developmental Disabilities
Results and Problems in Cell Differentiation | Year: 2012

Fragile X syndrome patients express a wide array of cognitive and other gender-specific phenotypic features. These manifestations result not only from molecular mechanisms that are altered as a result of the expansion of a CGG-repeat region in the FMR1 promoter, but also genetic factors such as founder effects and mosaicism. In this chapter, I will summarize the many and varied features of fragile X syndrome as they present themselves in a clinical setting and describe the procedures that are used to diagnose patients. Finally, I will briefly touch on recent developments that will affect patient screening in the future. © 2012 Springer-Verlag Berlin Heidelberg.

Reitz C.,Columbia University | Cheng R.,Columbia University | Schupf N.,Columbia University | Lee J.H.,Columbia University | And 6 more authors.
Neurobiology of Aging | Year: 2012

Genetic linkage and association studies in late-onset Alzheimer's disease (LOAD) or its endophenotypes have pointed to several regions on chromosome 10q, among these the ~ 250 kb linkage disequilibrium (LD) block harboring the genes IDE, KIF1, and HHEX. We explored the association between variants in the genomic region harboring the IDE-KIF11-HHEX complex with plasma Aβ40 and Aβ42 levels in a case-control cohort of Caribbean Hispanics. First, we performed single marker linear regression analysis relating the individual single nucleotide polymorphisms (SNPs) with plasma Aβ40 and Aβ42 levels. Then we performed 3-SNP sliding window haplotype analyses, correcting all analyses for multiple testing. Out of 32 SNPs in this region, 3 SNPs in IDE (rs2421943, rs12264682, rs11187060) were associated with plasma Aβ40 or Aβ42 levels in single marker and haplotype analyses after correction for multiple testing. All these SNPs lie within the same LD block, and are in LD with the previously reported haplotypes. Our findings provide support for an association in the IDE region on chromosome 10q with Aβ40 and 42 levels. © 2012 Elsevier Inc.

Pierpont E.I.,University of Wisconsin - Madison | Richmond E.K.,University of Wisconsin - Madison | Abbeduto L.,University of California at Davis | Kover S.T.,University of Wisconsin - Madison | Brown W.T.,Institute for Basic Research in Developmental Disabilities
Journal of Neurodevelopmental Disorders | Year: 2011

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. Although language delays are frequently observed in FXS, neither the longitudinal course of language development nor its cognitive predictors are well understood. The present study investigated whether phonological and working memory skills are predictive of growth in vocabulary and syntax in individuals with FXS during adolescence. Forty-four individuals with FXS (mean age = 12.61 years) completed assessments of phonological memory (nonword repetition and forward digit recall), verbal working memory (backward digit recall), vocabulary, syntax, and nonverbal cognition. Vocabulary and syntax skills were reassessed at a 2-year follow-up. In a series of analyses that controlled for nonverbal cognitive ability and severity of autism symptoms, the relative contributions of phonological and working memory to language change over time were investigated. These relationships were examined separately for boys and girls. In boys with FXS, phonological memory significantly predicted gains in vocabulary and syntax skills. Further, verbal working memory was uniquely associated with vocabulary gains among boys. In girls with FXS, phonological and working memory skills showed no relationship with language change across the 2-year time period. Our findings indicate that, for adolescent boys with FXS, acquisition of vocabulary and syntax may be constrained by the ability to maintain and manipulate phonological representations online. Implications for the identification and treatment of language disorders in this population are discussed. The present study is the first to identify specific cognitive mechanisms contributing to language growth over time in individuals with FXS. © 2011 Springer Science+Business Media, LLC.

Torr J.,Monash University | Strydom A.,University College London | Patti P.,Institute for Basic Research in Developmental Disabilities | Jokinen N.,University of Calgary
Journal of Policy and Practice in Intellectual Disabilities | Year: 2010

The life expectancy of adults with Down syndrome has increased dramatically over the last 30 years, leading to increasing numbers of adults with Down syndrome now living into middle and old age. Early-onset dementia of the Alzheimer type is highly prevalent in adults with Down syndrome in the sixth decade, and this has overshadowed other important conditions related to aging among adults with Down syndrome. The authors' aim was to update and summarize current knowledge on these conditions, and examine causes of morbidity and mortality in older people with Down syndrome by conducting a systematic review of the published literature for the period: 1993-2008. They reviewed English-language literature drawn from searches in the electronic databases Medline, CINAHL, and PsycINFO, as well as supplementary historical papers. The authors conclude that functional decline in older adults with Down syndrome cannot be assumed to be due only to dementia of the Alzheimer type (which is not inevitable in all adults with Down syndrome). Functional decline may be the result from a range of disorders, especially sensory and musculoskeletal impairments. Given the high rates of early-onset age-related disorders among adults with Down syndrome, programmatic screening, monitoring, and preventive interventions are required to limit secondary disabilities and premature mortality. With respect to assessment and treatment, in the absence of specialist disability physicians, geriatricians have a role to play. © 2010 International Association for the Scientific Study of Intellectual Disabilities and Wiley Periodicals, Inc.

McDuffie A.,University of Wisconsin - Madison | Abbeduto L.,University of Wisconsin - Madison | Lewis P.,University of Wisconsin - Madison | Kover S.,University of Wisconsin - Madison | And 3 more authors.
American Journal on Intellectual and Developmental Disabilities | Year: 2010

The Autism Diagnostic Interview-Revised (ADI-R) was used to examine diagnostic profiles and age-related changes in autism symptoms for a group of verbal children and adolescents who had fragile X syndrome, with and without autism. After controlling for nonverbal IQ, we found statistically significant between-group differences for lifetime and current autism symptoms for the Communication and Restricted Interests/Repetitive Behaviors domains, but not the Reciprocal Social Interaction domain. Effect sizes for differences in Reciprocal Social Interaction also were smaller than effect sizes for the other domains, with one exception. Overall, severity of autism symptoms improved with age for all participants, with the least improvement noted for Restricted Interests and Repetitive Behaviors. FMRP did not account for unique variance in autism symptoms over and above nonverbal IQ. © American Association on Intellectual and Developmental Disabilities.

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