Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study / Diandra BRKIĆ in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) Titre : Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study Type de document : texte imprimé Auteurs : Diandra BRKIĆ, Auteur ; Elise NG-CORDELL, Auteur ; Sinéad O'BRIEN, Auteur ; Gaia SCERIF, Auteur ; Duncan E. ASTLE, Auteur ; Kate BAKER, Auteur Langues : Anglais (eng) Mots-clés : Anxiety  Autism dimensions  Genetics  Hyperactivity  Intellectual disability Index. décimale : PER Périodiques Résumé : BACKGROUND: The relationships between specific genetic aetiology and phenotype in neurodevelopmental disorders are complex and hotly contested. Genes associated with intellectual disability (ID) can be grouped into networks according to gene function. This study explored whether individuals with ID show differences in autism spectrum characteristics (ASC), depending on the functional network membership of their rare, pathogenic de novo genetic variants. METHODS: Children and young people with ID of known genetic origin were allocated to two broad functional network groups: synaptic physiology (n = 29) or chromatin regulation (n = 23). We applied principle components analysis to the Social Responsiveness Scale to map the structure of ASC in this population and identified three components-Inflexibility, Social Understanding and Social Motivation. We then used Akaike information criterion to test the best fitting models for predicting ASC components, including demographic factors (age, gender), non-ASC behavioural factors (global adaptive function, anxiety, hyperactivity, inattention), and gene functional networks. RESULTS: We found that, when other factors are accounted for, the chromatin regulation group showed higher levels of Inflexibility. We also observed contrasting predictors of ASC within each network group. Within the chromatin regulation group, Social Understanding was associated with inattention, and Social Motivation was predicted by hyperactivity. Within the synaptic group, Social Understanding was associated with hyperactivity, and Social Motivation was linked to anxiety. LIMITATIONS: Functional network definitions were manually curated based on multiple sources of evidence, but a data-driven approach to classification may be more robust. Sample sizes for rare genetic diagnoses remain small, mitigated by our network-based approach to group comparisons. This is a cross-sectional study across a wide age range, and longitudinal data within focused age groups will be informative of developmental trajectories across network groups. CONCLUSION: We report that gene functional networks can predict Inflexibility, but not other ASC dimensions. Contrasting behavioural associations within each group suggest network-specific developmental pathways from genomic variation to autism. Simple classification of neurodevelopmental disorder genes as high risk or low risk for autism is unlikely to be valid or useful. En ligne : http://dx.doi.org/10.1186/s13229-020-00403-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438 [article] Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study [texte imprimé] / Diandra BRKIĆ, Auteur ; Elise NG-CORDELL, Auteur ; Sinéad O'BRIEN, Auteur ; Gaia SCERIF, Auteur ; Duncan E. ASTLE, Auteur ; Kate BAKER, Auteur. Langues : Anglais (eng) in Molecular Autism > 11 (2020) Mots-clés : Anxiety  Autism dimensions  Genetics  Hyperactivity  Intellectual disability Index. décimale : PER Périodiques Résumé : BACKGROUND: The relationships between specific genetic aetiology and phenotype in neurodevelopmental disorders are complex and hotly contested. Genes associated with intellectual disability (ID) can be grouped into networks according to gene function. This study explored whether individuals with ID show differences in autism spectrum characteristics (ASC), depending on the functional network membership of their rare, pathogenic de novo genetic variants. METHODS: Children and young people with ID of known genetic origin were allocated to two broad functional network groups: synaptic physiology (n = 29) or chromatin regulation (n = 23). We applied principle components analysis to the Social Responsiveness Scale to map the structure of ASC in this population and identified three components-Inflexibility, Social Understanding and Social Motivation. We then used Akaike information criterion to test the best fitting models for predicting ASC components, including demographic factors (age, gender), non-ASC behavioural factors (global adaptive function, anxiety, hyperactivity, inattention), and gene functional networks. RESULTS: We found that, when other factors are accounted for, the chromatin regulation group showed higher levels of Inflexibility. We also observed contrasting predictors of ASC within each network group. Within the chromatin regulation group, Social Understanding was associated with inattention, and Social Motivation was predicted by hyperactivity. Within the synaptic group, Social Understanding was associated with hyperactivity, and Social Motivation was linked to anxiety. LIMITATIONS: Functional network definitions were manually curated based on multiple sources of evidence, but a data-driven approach to classification may be more robust. Sample sizes for rare genetic diagnoses remain small, mitigated by our network-based approach to group comparisons. This is a cross-sectional study across a wide age range, and longitudinal data within focused age groups will be informative of developmental trajectories across network groups. CONCLUSION: We report that gene functional networks can predict Inflexibility, but not other ASC dimensions. Contrasting behavioural associations within each group suggest network-specific developmental pathways from genomic variation to autism. Simple classification of neurodevelopmental disorder genes as high risk or low risk for autism is unlikely to be valid or useful. En ligne : http://dx.doi.org/10.1186/s13229-020-00403-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438

In Our Own Words: The Complex Sensory Experiences of Autistic Adults / Keren MACLENNAN in Journal of Autism and Developmental Disorders, 52-7 (July 2022)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 52-7 (July 2022) . - p.3061-3075 Titre : In Our Own Words: The Complex Sensory Experiences of Autistic Adults Type de document : texte imprimé Auteurs : Keren MACLENNAN, Auteur ; Sinéad O'BRIEN, Auteur ; Teresa TAVASSOLI, Auteur Article en page(s) : p.3061-3075 Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder/complications  Autistic Disorder/complications  Humans  Quality of Life  Surveys and Questionnaires  Autism  Autistic  Participatory  Qualitative  Sensory  content of this article. Index. décimale : PER Périodiques Résumé : Autistic adults commonly experience sensory reactivity differences. Sensory hyperreactivity is frequently researched, whilst hyporeactivity and seeking, and experiences across domains, e.g., vision, are often neglected. Therefore, we aimed to understand more about the sensory experiences of autistic adults. We conducted a mixed-methods study, co-produced with stakeholders; recruiting 49 autistic adults who completed an online survey. Firstly, quantitative results and content analysis enhanced our understanding of sensory input/contexts associated with sensory hyperreactivity, hyporeactivity, and seeking across modalities. Secondly, thematic analysis developed themes relating to 'Outcomes', 'Control', 'Tolerance and management', and 'The role of other people', informing a theoretical model of sensory reactivity differences in autistic adults. These findings have implications for support services and improving quality of life for autistic adults. En ligne : http://dx.doi.org/10.1007/s10803-021-05186-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 [article] In Our Own Words: The Complex Sensory Experiences of Autistic Adults [texte imprimé] / Keren MACLENNAN, Auteur ; Sinéad O'BRIEN, Auteur ; Teresa TAVASSOLI, Auteur . - p.3061-3075. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 52-7 (July 2022) . - p.3061-3075 Mots-clés : Adult  Autism Spectrum Disorder/complications  Autistic Disorder/complications  Humans  Quality of Life  Surveys and Questionnaires  Autism  Autistic  Participatory  Qualitative  Sensory  content of this article. Index. décimale : PER Périodiques Résumé : Autistic adults commonly experience sensory reactivity differences. Sensory hyperreactivity is frequently researched, whilst hyporeactivity and seeking, and experiences across domains, e.g., vision, are often neglected. Therefore, we aimed to understand more about the sensory experiences of autistic adults. We conducted a mixed-methods study, co-produced with stakeholders; recruiting 49 autistic adults who completed an online survey. Firstly, quantitative results and content analysis enhanced our understanding of sensory input/contexts associated with sensory hyperreactivity, hyporeactivity, and seeking across modalities. Secondly, thematic analysis developed themes relating to 'Outcomes', 'Control', 'Tolerance and management', and 'The role of other people', informing a theoretical model of sensory reactivity differences in autistic adults. These findings have implications for support services and improving quality of life for autistic adults. En ligne : http://dx.doi.org/10.1007/s10803-021-05186-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477

Social and emotional characteristics of girls and young women with DDX3X-associated intellectual disability: a descriptive and comparative study / Elise NG-CORDELL in Journal of Autism and Developmental Disorders, 53-8 (August 2023)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 53-8 (August 2023) . - p.3208-3219 Titre : Social and emotional characteristics of girls and young women with DDX3X-associated intellectual disability: a descriptive and comparative study Type de document : texte imprimé Auteurs : Elise NG-CORDELL, Auteur ; Anna KOLESNIK-TAYLOR, Auteur ; Sinéad O'BRIEN, Auteur ; Duncan E. ASTLE, Auteur ; Gaia SCERIF, Auteur ; Kate BAKER, Auteur Article en page(s) : p.3208-3219 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : DDX3X variants are a common cause of intellectual disability (ID) in females, and have been associated with autism spectrum disorder and emotional-behavioural difficulties. In this study, we compared phenotypic data for 23 females with DDX3X variants, to 23 females with ID and other genetic diagnoses. We found a wide range of adaptive, social and emotional function within the DDX3X group. Autism characteristics did not differ between DDX3X and comparison groups, while levels of anxiety and self-injurious behaviour (SIB) were significantly higher in the DDX3X group. Within the DDX3X group, adaptive function, autism characteristics, anxiety and SIB scores were positively correlated, with evidence for group-specific associations with SIB. Future work is warranted to explore the multilevel mechanisms contributing to social and emotional development in individuals with DDX3X variants. En ligne : https://doi.org/10.1007/s10803-022-05527-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=508 [article] Social and emotional characteristics of girls and young women with DDX3X-associated intellectual disability: a descriptive and comparative study [texte imprimé] / Elise NG-CORDELL, Auteur ; Anna KOLESNIK-TAYLOR, Auteur ; Sinéad O'BRIEN, Auteur ; Duncan E. ASTLE, Auteur ; Gaia SCERIF, Auteur ; Kate BAKER, Auteur . - p.3208-3219. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 53-8 (August 2023) . - p.3208-3219 Index. décimale : PER Périodiques Résumé : DDX3X variants are a common cause of intellectual disability (ID) in females, and have been associated with autism spectrum disorder and emotional-behavioural difficulties. In this study, we compared phenotypic data for 23 females with DDX3X variants, to 23 females with ID and other genetic diagnoses. We found a wide range of adaptive, social and emotional function within the DDX3X group. Autism characteristics did not differ between DDX3X and comparison groups, while levels of anxiety and self-injurious behaviour (SIB) were significantly higher in the DDX3X group. Within the DDX3X group, adaptive function, autism characteristics, anxiety and SIB scores were positively correlated, with evidence for group-specific associations with SIB. Future work is warranted to explore the multilevel mechanisms contributing to social and emotional development in individuals with DDX3X variants. En ligne : https://doi.org/10.1007/s10803-022-05527-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=508

STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics / Sinéad O'BRIEN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 17 p. Titre : STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics Type de document : texte imprimé Auteurs : Sinéad O'BRIEN, Auteur ; Elise NG-CORDELL, Auteur ; Duncan E. ASTLE, Auteur ; Gaia SCERIF, Auteur ; Kate BAKER, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Mots-clés : Epilepsy  Intellectual disability  Language  Stxbp1  Social Index. décimale : PER Périodiques Résumé : BACKGROUND: De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. METHODS: To address this, we collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics. Participants were 14 individuals with STXBP1-associated neurodevelopmental disorder, ascertained from clinical genetics and neurology services UK-wide. Data was collected via standardised questionnaires administered to parents at home, supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes (ID group). To account for the potential impact of global cognitive impairment, a secondary comparison was made to an ability-matched subset of the ID group (low-ability ID group). RESULTS: The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. In comparison to the low-ability ID group, severity of receptive language and social impairments discriminated the STXBP1 group. A striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation. CONCLUSIONS: De novo mutations in STXBP1 are associated with complex and variable neurodevelopmental impairments. Consistent features, which discriminate this disorder from other monogenic causes of ID, are severe language impairment and difficulties managing social interactions, despite strong social motivation. Future work could explore the physiological mechanisms linking motor, speech, and social development in this disorder. Understanding the developmental emergence of behavioural characteristics can help to focus clinical assessment and management after genetic diagnosis, with the long-term aim of improving outcomes for patients and families. En ligne : https://dx.doi.org/10.1186/s11689-019-9278-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics [texte imprimé] / Sinéad O'BRIEN, Auteur ; Elise NG-CORDELL, Auteur ; Duncan E. ASTLE, Auteur ; Gaia SCERIF, Auteur ; Kate BAKER, Auteur . - 17 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 17 p. Mots-clés : Epilepsy  Intellectual disability  Language  Stxbp1  Social Index. décimale : PER Périodiques Résumé : BACKGROUND: De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. METHODS: To address this, we collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics. Participants were 14 individuals with STXBP1-associated neurodevelopmental disorder, ascertained from clinical genetics and neurology services UK-wide. Data was collected via standardised questionnaires administered to parents at home, supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes (ID group). To account for the potential impact of global cognitive impairment, a secondary comparison was made to an ability-matched subset of the ID group (low-ability ID group). RESULTS: The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. In comparison to the low-ability ID group, severity of receptive language and social impairments discriminated the STXBP1 group. A striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation. CONCLUSIONS: De novo mutations in STXBP1 are associated with complex and variable neurodevelopmental impairments. Consistent features, which discriminate this disorder from other monogenic causes of ID, are severe language impairment and difficulties managing social interactions, despite strong social motivation. Future work could explore the physiological mechanisms linking motor, speech, and social development in this disorder. Understanding the developmental emergence of behavioural characteristics can help to focus clinical assessment and management after genetic diagnosis, with the long-term aim of improving outcomes for patients and families. En ligne : https://dx.doi.org/10.1186/s11689-019-9278-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

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