Browsing by Subject "Intellectual Disability"

Now showing 1 - 4 of 4
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    Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression.
    (Molecular autism, 2016-01) Casanova, Emily L; Sharp, Julia L; Chakraborty, Hrishikesh; Sumi, Nahid Sultana; Casanova, Manuel F
    BACKGROUND:Intellectual disability (ID), autism, and epilepsy share frequent yet variable comorbidities with one another. In order to better understand potential genetic divergence underlying this variable risk, we studied genes responsible for monogenic IDs, grouped according to their autism and epilepsy comorbidities. METHODS:Utilizing 465 different forms of ID with known molecular origins, we accessed available genetic databases in conjunction with gene ontology (GO) to determine whether the genetics underlying ID diverge according to its comorbidities with autism and epilepsy and if genes highly penetrant for autism or epilepsy share distinctive features that set them apart from genes that confer comparatively variable or no apparent risk. RESULTS:The genetics of ID with autism are relatively enriched in terms associated with nervous system-specific processes and structural morphogenesis. In contrast, we find that ID with highly comorbid epilepsy (HCE) is modestly associated with lipid metabolic processes while ID without autism or epilepsy comorbidity (ID only) is enriched at the Golgi membrane. Highly comorbid autism (HCA) genes, on the other hand, are strongly enriched within the nucleus, are typically involved in regulation of gene expression, and, along with IDs with more variable autism, share strong ties with a core protein-protein interaction (PPI) network integral to basic patterning of the CNS. CONCLUSIONS:According to GO terminology, autism-related gene products are integral to neural development. While it is difficult to draw firm conclusions regarding IDs unassociated with autism, it is clear that the majority of HCA genes are tightly linked with general dysregulation of gene expression, suggesting that disturbances to the chronology of neural maturation and patterning may be key in conferring susceptibility to autism spectrum conditions.
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    Genetic disruption of WASHC4 drives endo-lysosomal dysfunction and cognitive-movement impairments in mice and humans.
    (eLife, 2021-03-22) Courtland, Jamie L; Bradshaw, Tyler Wa; Waitt, Greg; Soderblom, Erik J; Ho, Tricia; Rajab, Anna; Vancini, Ricardo; Kim, Il Hwan; Soderling, Scott H
    Mutation of the Wiskott-Aldrich syndrome protein and SCAR homology (WASH) complex subunit, SWIP, is implicated in human intellectual disability, but the cellular etiology of this association is unknown. We identify the neuronal WASH complex proteome, revealing a network of endosomal proteins. To uncover how dysfunction of endosomal SWIP leads to disease, we generate a mouse model of the human WASHC4c.3056C>G mutation. Quantitative spatial proteomics analysis of SWIPP1019R mouse brain reveals that this mutation destabilizes the WASH complex and uncovers significant perturbations in both endosomal and lysosomal pathways. Cellular and histological analyses confirm that SWIPP1019R results in endo-lysosomal disruption and uncover indicators of neurodegeneration. We find that SWIPP1019R not only impacts cognition, but also causes significant progressive motor deficits in mice. A retrospective analysis of SWIPP1019R patients reveals similar movement deficits in humans. Combined, these findings support the model that WASH complex destabilization, resulting from SWIPP1019R, drives cognitive and motor impairments via endo-lysosomal dysfunction in the brain.
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    Story recall by mentally retarded children.
    (Psychol Rep, 1983-12) Bacon, EH; Rubin, David C
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    Substance abuse among individuals with intellectual disabilities.
    (Research in developmental disabilities, 2012-07) Carroll Chapman, Shawna L; Wu, Li-Tzy
    Individuals with disabilities are a growing population that confronts multiple disadvantages from social and environmental determinants of health. In particular, the 7-8 million people in the U.S. with an intellectual disability (ID) suffer disproportionately from substance use problems, largely because of a lack of empirical evidence to inform prevention and treatment efforts for them. Although available research could inform future research efforts, studies are scattered across disciplines with the last review synthesizing findings written more than five years ago. To consider more recent findings with earlier works, PubMed, PsychINFO, and Google Scholar were searched and produced 37 peer-reviewed texts across multiple disciplines, 15 from 2006 or later. While the prevalence of alcohol and illicit drug use in this population are low, the risk of having a substance-related problem among ID substance users is comparatively high. Gaps in the research and population subgroups that warrant special attention are identified, such as individuals with borderline and mild ID, individuals with co-occurring mental illness, and individuals who are incarcerated. Compared with substance abusers without ID, ID substance abusers are less likely to receive substance abuse treatment or remain in treatment. Research is needed to better gauge the magnitude of substance use problems, identify prevention strategies, and specify treatment components that meet the unique needs of individuals with ID.