Exploring autism symptoms in an Australian cohort of patients with Prader-Willi and Angelman syndromes / E. K. BAKER in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 24 p. Titre : Exploring autism symptoms in an Australian cohort of patients with Prader-Willi and Angelman syndromes Type de document : Texte imprimé et/ou numérique Auteurs : E. K. BAKER, Auteur ; D. E. GODLER, Auteur ; M. BUI, Auteur ; C. HICKERTON, Auteur ; C. ROGERS, Auteur ; M. FIELD, Auteur ; D. J. AMOR, Auteur ; L. BRETHERTON, Auteur Année de publication : 2018 Article en page(s) : 24 p. Langues : Anglais (eng) Mots-clés : Ados  Angelman syndrome  Autism  Iq  Prader-Willi syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurodevelopmental disorders that are caused by abnormal expression of imprinted genes in the 15q11-13 region. Dysregulation of genes located in this region has been proposed as a susceptibility factor for autism spectrum disorder (ASD) in both disorders. METHODS: This study aimed to explore symptoms of ASD in 25 PWS and 19 AS individuals aged between 1 and 39 years via objective assessment. Participants completed the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) and a developmentally or age-appropriate intellectual functioning assessment. All participants had their genetic diagnosis confirmed using DNA methylation analysis and microarray testing of copy number changes within the 15q11-13 region. RESULTS: Participants with PWS had significantly higher overall and social affect calibrated severity scores (CSS) on the ADOS-2 compared to AS participants (p = .0055 and .0015, respectively), but the two groups did not differ significantly on CSS for the repetitive and restricted behaviour domain. CONCLUSIONS: PWS cases presented with greater symptoms associated with ASD compared to individuals with AS. Mental health issues associated with PWS may contribute to elevated symptoms of ASD, particularly in adolescents and adults with PWS. En ligne : http://dx.doi.org/10.1186/s11689-018-9242-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Exploring autism symptoms in an Australian cohort of patients with Prader-Willi and Angelman syndromes [Texte imprimé et/ou numérique] / E. K. BAKER, Auteur ; D. E. GODLER, Auteur ; M. BUI, Auteur ; C. HICKERTON, Auteur ; C. ROGERS, Auteur ; M. FIELD, Auteur ; D. J. AMOR, Auteur ; L. BRETHERTON, Auteur . - 2018 . - 24 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 24 p. Mots-clés : Ados  Angelman syndrome  Autism  Iq  Prader-Willi syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurodevelopmental disorders that are caused by abnormal expression of imprinted genes in the 15q11-13 region. Dysregulation of genes located in this region has been proposed as a susceptibility factor for autism spectrum disorder (ASD) in both disorders. METHODS: This study aimed to explore symptoms of ASD in 25 PWS and 19 AS individuals aged between 1 and 39 years via objective assessment. Participants completed the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) and a developmentally or age-appropriate intellectual functioning assessment. All participants had their genetic diagnosis confirmed using DNA methylation analysis and microarray testing of copy number changes within the 15q11-13 region. RESULTS: Participants with PWS had significantly higher overall and social affect calibrated severity scores (CSS) on the ADOS-2 compared to AS participants (p = .0055 and .0015, respectively), but the two groups did not differ significantly on CSS for the repetitive and restricted behaviour domain. CONCLUSIONS: PWS cases presented with greater symptoms associated with ASD compared to individuals with AS. Mental health issues associated with PWS may contribute to elevated symptoms of ASD, particularly in adolescents and adults with PWS. En ligne : http://dx.doi.org/10.1186/s11689-018-9242-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features / E. K. BAKER in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 21 p. Titre : Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features Type de document : Texte imprimé et/ou numérique Auteurs : E. K. BAKER, Auteur ; M. ARPONE, Auteur ; S. M. ALIAGA, Auteur ; L. BRETHERTON, Auteur ; C. M. KRAAN, Auteur ; M. BUI, Auteur ; H. R. SLATER, Auteur ; L. LING, Auteur ; D. FRANCIS, Auteur ; M. F. HUNTER, Auteur ; J. ELLIOTT, Auteur ; C. ROGERS, Auteur ; M. FIELD, Auteur ; J. COHEN, Auteur ; Kim CORNISH, Auteur ; L. SANTA MARIA, Auteur ; V. FAUNDES, Auteur ; B. CUROTTO, Auteur ; P. MORALES, Auteur ; C. TRIGO, Auteur ; I. SALAS, Auteur ; A. M. ALLIENDE, Auteur ; D. J. AMOR, Auteur ; D. E. GODLER, Auteur Article en page(s) : 21 p. Langues : Anglais (eng) Mots-clés : Autism  FMR1 mRNA  Fragile X syndrome  Intellectual disability  Mosaicism Index. décimale : PER Périodiques Résumé : Background: Fragile X syndrome (FXS) is a common monogenic cause of intellectual disability with autism features. While it is caused by loss of the FMR1 product (FMRP), mosaicism for active and inactive FMR1 alleles, including alleles termed premutation (PM: 55-199 CGGs), is not uncommon. Importantly, both PM and active full mutation (FM: >/= 200 CGGs) alleles often express elevated levels of mRNA that are thought to be toxic. This study determined if complete FMR1 mRNA silencing from FM alleles and/or levels of FMR1 mRNA (if present) in blood are associated with intellectual functioning and autism features in FXS. Methods: The study cohort included 98 participants (70.4% male) with FXS (FM-only and PM/FM mosaic) aged 1-43 years. A control group of 14 females were used to establish control FMR1 mRNA reference range. Intellectual functioning and autism features were assessed using the Mullen Scales of Early Learning or an age-appropriate Wechsler Scale and the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2), respectively. FMR1 mRNA was analysed in venous blood collected at the time of assessments, using the real-time PCR relative standard curve method. Results: Females with FXS had significantly higher levels of FMR1 mRNA (p < 0.001) than males. FMR1 mRNA levels were positively associated with age (p < 0.001), but not with intellectual functioning and autistic features in females. FM-only males (aged < 19 years) expressing FM FMR1 mRNA had significantly higher ADOS calibrated severity scores compared to FM-only males with completely silenced FMR1 (p = 0.011). However, there were no significant differences between these subgroups on intellectual functioning. In contrast, decreased levels of FMR1 mRNA were associated with decreased intellectual functioning in FXS males (p = 0.029), but not autism features, when combined with the PM/FM mosaic group. Conclusion: Incomplete silencing of toxic FM RNA may be associated with autistic features, but not intellectual functioning in FXS males. While decreased levels of mRNA may be more predictive of intellectual functioning than autism features. If confirmed in future studies, these findings may have implications for patient stratification, outcome measure development, and design of clinical and pre-clinical trials in FXS. En ligne : http://dx.doi.org/10.1186/s13229-019-0271-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398 [article] Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features [Texte imprimé et/ou numérique] / E. K. BAKER, Auteur ; M. ARPONE, Auteur ; S. M. ALIAGA, Auteur ; L. BRETHERTON, Auteur ; C. M. KRAAN, Auteur ; M. BUI, Auteur ; H. R. SLATER, Auteur ; L. LING, Auteur ; D. FRANCIS, Auteur ; M. F. HUNTER, Auteur ; J. ELLIOTT, Auteur ; C. ROGERS, Auteur ; M. FIELD, Auteur ; J. COHEN, Auteur ; Kim CORNISH, Auteur ; L. SANTA MARIA, Auteur ; V. FAUNDES, Auteur ; B. CUROTTO, Auteur ; P. MORALES, Auteur ; C. TRIGO, Auteur ; I. SALAS, Auteur ; A. M. ALLIENDE, Auteur ; D. J. AMOR, Auteur ; D. E. GODLER, Auteur . - 21 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 21 p. Mots-clés : Autism  FMR1 mRNA  Fragile X syndrome  Intellectual disability  Mosaicism Index. décimale : PER Périodiques Résumé : Background: Fragile X syndrome (FXS) is a common monogenic cause of intellectual disability with autism features. While it is caused by loss of the FMR1 product (FMRP), mosaicism for active and inactive FMR1 alleles, including alleles termed premutation (PM: 55-199 CGGs), is not uncommon. Importantly, both PM and active full mutation (FM: >/= 200 CGGs) alleles often express elevated levels of mRNA that are thought to be toxic. This study determined if complete FMR1 mRNA silencing from FM alleles and/or levels of FMR1 mRNA (if present) in blood are associated with intellectual functioning and autism features in FXS. Methods: The study cohort included 98 participants (70.4% male) with FXS (FM-only and PM/FM mosaic) aged 1-43 years. A control group of 14 females were used to establish control FMR1 mRNA reference range. Intellectual functioning and autism features were assessed using the Mullen Scales of Early Learning or an age-appropriate Wechsler Scale and the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2), respectively. FMR1 mRNA was analysed in venous blood collected at the time of assessments, using the real-time PCR relative standard curve method. Results: Females with FXS had significantly higher levels of FMR1 mRNA (p < 0.001) than males. FMR1 mRNA levels were positively associated with age (p < 0.001), but not with intellectual functioning and autistic features in females. FM-only males (aged < 19 years) expressing FM FMR1 mRNA had significantly higher ADOS calibrated severity scores compared to FM-only males with completely silenced FMR1 (p = 0.011). However, there were no significant differences between these subgroups on intellectual functioning. In contrast, decreased levels of FMR1 mRNA were associated with decreased intellectual functioning in FXS males (p = 0.029), but not autism features, when combined with the PM/FM mosaic group. Conclusion: Incomplete silencing of toxic FM RNA may be associated with autistic features, but not intellectual functioning in FXS males. While decreased levels of mRNA may be more predictive of intellectual functioning than autism features. If confirmed in future studies, these findings may have implications for patient stratification, outcome measure development, and design of clinical and pre-clinical trials in FXS. En ligne : http://dx.doi.org/10.1186/s13229-019-0271-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=398

A systematic review of brain MRI findings in monogenic disorders strongly associated with autism spectrum disorder / V. FREWER in Journal of Child Psychology and Psychiatry, 62-11 (November 2021)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 62-11 (November 2021) . - p.1339-1352 Titre : A systematic review of brain MRI findings in monogenic disorders strongly associated with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : V. FREWER, Auteur ; C. P. GILCHRIST, Auteur ; S. E. COLLINS, Auteur ; K. WILLIAMS, Auteur ; M. L. SEAL, Auteur ; R. J. LEVENTER, Auteur ; D. J. AMOR, Auteur Article en page(s) : p.1339-1352 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnostic imaging/genetics  Autistic Disorder  Brain/diagnostic imaging  Humans  Magnetic Resonance Imaging  Neuroimaging  Autism spectrum disorder  Mri  magnetic resonance imaging  monogenic disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: Research on monogenic forms of autism spectrum disorder (autism) can inform our understanding of genetic contributions to the autism phenotype; yet, there is much to be learned about the pathways from gene to brain structure to behavior. This systematic review summarizes and evaluates research on brain magnetic resonance imaging (MRI) findings in monogenic conditions that have strong association with autism. This will improve understanding of the impact of genetic variability on brain structure and related behavioral traits in autism. METHODS: The search strategy for this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias (ROB) assessment was completed on included studies using the Newcastle-Ottawa Scales. RESULTS: Of 4,287 studies screened, 69 were included pertaining to 13 of the top 20 genes with the strongest association with autism. The greatest number of studies related to individuals with PTEN variants and autism. Brain MRI abnormalities were reported for 12 of the 13 genes studied, and in 51.7% of participants across all 13 genes, including 100% of participants with ARID1B variants. Specific MRI findings were highly variable, with no clear patterns emerging within or between the 13 genes, although white matter abnormalities were the most common. Few studies reported specific details about methods for acquisition and processing of brain MRI, and descriptors for brain abnormalities were variable. ROB assessment indicated high ROB for all studies, largely due to small sample sizes and lack of comparison groups. CONCLUSIONS: Brain abnormalities are common in this population of individuals, in particular, children; however, a range of different brain abnormalities were reported within and between genes. Directions for future neuroimaging research in monogenic autism are suggested. En ligne : http://dx.doi.org/10.1111/jcpp.13510 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456 [article] A systematic review of brain MRI findings in monogenic disorders strongly associated with autism spectrum disorder [Texte imprimé et/ou numérique] / V. FREWER, Auteur ; C. P. GILCHRIST, Auteur ; S. E. COLLINS, Auteur ; K. WILLIAMS, Auteur ; M. L. SEAL, Auteur ; R. J. LEVENTER, Auteur ; D. J. AMOR, Auteur . - p.1339-1352. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 62-11 (November 2021) . - p.1339-1352 Mots-clés : Autism Spectrum Disorder/diagnostic imaging/genetics  Autistic Disorder  Brain/diagnostic imaging  Humans  Magnetic Resonance Imaging  Neuroimaging  Autism spectrum disorder  Mri  magnetic resonance imaging  monogenic disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: Research on monogenic forms of autism spectrum disorder (autism) can inform our understanding of genetic contributions to the autism phenotype; yet, there is much to be learned about the pathways from gene to brain structure to behavior. This systematic review summarizes and evaluates research on brain magnetic resonance imaging (MRI) findings in monogenic conditions that have strong association with autism. This will improve understanding of the impact of genetic variability on brain structure and related behavioral traits in autism. METHODS: The search strategy for this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias (ROB) assessment was completed on included studies using the Newcastle-Ottawa Scales. RESULTS: Of 4,287 studies screened, 69 were included pertaining to 13 of the top 20 genes with the strongest association with autism. The greatest number of studies related to individuals with PTEN variants and autism. Brain MRI abnormalities were reported for 12 of the 13 genes studied, and in 51.7% of participants across all 13 genes, including 100% of participants with ARID1B variants. Specific MRI findings were highly variable, with no clear patterns emerging within or between the 13 genes, although white matter abnormalities were the most common. Few studies reported specific details about methods for acquisition and processing of brain MRI, and descriptors for brain abnormalities were variable. ROB assessment indicated high ROB for all studies, largely due to small sample sizes and lack of comparison groups. CONCLUSIONS: Brain abnormalities are common in this population of individuals, in particular, children; however, a range of different brain abnormalities were reported within and between genes. Directions for future neuroimaging research in monogenic autism are suggested. En ligne : http://dx.doi.org/10.1111/jcpp.13510 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456

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