Characterizing Sensory Phenotypes of Subgroups with a Known Genetic Etiology Pertaining to Diagnoses of Autism Spectrum Disorder and Intellectual Disability / Caitlin M. HUDAC in Journal of Autism and Developmental Disorders, 54-6 (June 2024)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 54-6 (June 2024) . - p.2386-2401 Titre : Characterizing Sensory Phenotypes of Subgroups with a Known Genetic Etiology Pertaining to Diagnoses of Autism Spectrum Disorder and Intellectual Disability Type de document : Texte imprimé et/ou numérique Auteurs : Caitlin M. HUDAC, Auteur ; Nicole R. FRIEDMAN, Auteur ; Victoria R. WARD, Auteur ; Rachel E. ESTREICHER, Auteur ; Grace C. DORSEY, Auteur ; Raphael A. BERNIER, Auteur ; Evangeline C. KURTZ-NELSON, Auteur ; Rachel K. EARL, Auteur ; Evan E. EICHLER, Auteur ; Emily NEUHAUS, Auteur Article en page(s) : p.2386-2401 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : We aimed to identify unique constellations of sensory phenotypes for genetic etiologies associated with diagnoses of autism spectrum disorder (ASD) and intellectual disability (ID). Caregivers reported on sensory behaviors via the Sensory Profile for 290 participants (younger than 25 years of age) with ASD and/or ID diagnoses, of which?~?70% have a known pathogenic genetic etiology. Caregivers endorsed poor registration (i.e., high sensory threshold, passive behaviors) for all genetic subgroups relative to an "idiopathic" comparison group with an ASD diagnosis and without a known genetic etiology. Genetic profiles indicated prominent sensory seeking in ADNP, CHD8, and DYRK1A, prominent sensory sensitivities in SCN2A, and fewer sensation avoidance behaviors in GRIN2B (relative to the idiopathic ASD comparison group). En ligne : https://doi.org/10.1007/s10803-023-05897-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=530 [article] Characterizing Sensory Phenotypes of Subgroups with a Known Genetic Etiology Pertaining to Diagnoses of Autism Spectrum Disorder and Intellectual Disability [Texte imprimé et/ou numérique] / Caitlin M. HUDAC, Auteur ; Nicole R. FRIEDMAN, Auteur ; Victoria R. WARD, Auteur ; Rachel E. ESTREICHER, Auteur ; Grace C. DORSEY, Auteur ; Raphael A. BERNIER, Auteur ; Evangeline C. KURTZ-NELSON, Auteur ; Rachel K. EARL, Auteur ; Evan E. EICHLER, Auteur ; Emily NEUHAUS, Auteur . - p.2386-2401. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 54-6 (June 2024) . - p.2386-2401 Index. décimale : PER Périodiques Résumé : We aimed to identify unique constellations of sensory phenotypes for genetic etiologies associated with diagnoses of autism spectrum disorder (ASD) and intellectual disability (ID). Caregivers reported on sensory behaviors via the Sensory Profile for 290 participants (younger than 25 years of age) with ASD and/or ID diagnoses, of which?~?70% have a known pathogenic genetic etiology. Caregivers endorsed poor registration (i.e., high sensory threshold, passive behaviors) for all genetic subgroups relative to an "idiopathic" comparison group with an ASD diagnosis and without a known genetic etiology. Genetic profiles indicated prominent sensory seeking in ADNP, CHD8, and DYRK1A, prominent sensory sensitivities in SCN2A, and fewer sensation avoidance behaviors in GRIN2B (relative to the idiopathic ASD comparison group). En ligne : https://doi.org/10.1007/s10803-023-05897-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=530

Characterizing the autism spectrum phenotype in DYRK1A-related syndrome / Evangeline C. KURTZ-NELSON in Autism Research, 16-8 (August 2023)  

Public ISBD [article]  inAutism Research > 16-8 (August 2023) . - p.1488-1500 Titre : Characterizing the autism spectrum phenotype in DYRK1A-related syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Evangeline C. KURTZ-NELSON, Auteur ; Hannah M. REA, Auteur ; Aiva C. PETRICEKS, Auteur ; Caitlin M. HUDAC, Auteur ; Tianyun WANG, Auteur ; Rachel K. EARL, Auteur ; Raphael A. BERNIER, Auteur ; Evan E. EICHLER, Auteur ; Emily NEUHAUS, Auteur Article en page(s) : p.1488-1500 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Likely gene-disrupting (LGD) variants in DYRK1A are causative of DYRK1A syndrome and associated with autism spectrum disorder (ASD) and intellectual disability (ID). While many individuals with DYRK1A syndrome are diagnosed with ASD, they may present with a unique profile of ASD traits. We present a comprehensive characterization of the ASD profile in children and young adults with LGDs in DYRK1A. Individuals with LGD variants in DYRK1A (n=29) were compared to children who had ASD with no known genetic cause, either with low nonverbal IQ (n=14) or average or above nonverbal IQ (n=41). ASD was assessed using the ADOS-2, ADI-R, SRS-2, SCQ, and RBS-R. Quantitative score comparisons were conducted, as were qualitative analyses of clinicians' behavioral observations. Diagnosis of ASD was confirmed in 85% and ID was confirmed in 89% of participants with DYRK1A syndrome. Individuals with DYRK1A syndrome showed broadly similar social communication behaviors to children with idiopathic ASD and below-average nonverbal IQ, with specific challenges noted in social reciprocity and nonverbal communication. Children with DYRK1A syndrome also showed high rates of sensory-seeking behaviors. Phenotypic characterization of individuals with DYRK1A syndrome may provide additional information on mechanisms contributing to co-occurring ASD and ID and contribute to the identification of genetic predictors of specific ASD traits. En ligne : https://doi.org/10.1002/aur.2995 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=510 [article] Characterizing the autism spectrum phenotype in DYRK1A-related syndrome [Texte imprimé et/ou numérique] / Evangeline C. KURTZ-NELSON, Auteur ; Hannah M. REA, Auteur ; Aiva C. PETRICEKS, Auteur ; Caitlin M. HUDAC, Auteur ; Tianyun WANG, Auteur ; Rachel K. EARL, Auteur ; Raphael A. BERNIER, Auteur ; Evan E. EICHLER, Auteur ; Emily NEUHAUS, Auteur . - p.1488-1500. Langues : Anglais (eng) in Autism Research > 16-8 (August 2023) . - p.1488-1500 Index. décimale : PER Périodiques Résumé : Abstract Likely gene-disrupting (LGD) variants in DYRK1A are causative of DYRK1A syndrome and associated with autism spectrum disorder (ASD) and intellectual disability (ID). While many individuals with DYRK1A syndrome are diagnosed with ASD, they may present with a unique profile of ASD traits. We present a comprehensive characterization of the ASD profile in children and young adults with LGDs in DYRK1A. Individuals with LGD variants in DYRK1A (n=29) were compared to children who had ASD with no known genetic cause, either with low nonverbal IQ (n=14) or average or above nonverbal IQ (n=41). ASD was assessed using the ADOS-2, ADI-R, SRS-2, SCQ, and RBS-R. Quantitative score comparisons were conducted, as were qualitative analyses of clinicians' behavioral observations. Diagnosis of ASD was confirmed in 85% and ID was confirmed in 89% of participants with DYRK1A syndrome. Individuals with DYRK1A syndrome showed broadly similar social communication behaviors to children with idiopathic ASD and below-average nonverbal IQ, with specific challenges noted in social reciprocity and nonverbal communication. Children with DYRK1A syndrome also showed high rates of sensory-seeking behaviors. Phenotypic characterization of individuals with DYRK1A syndrome may provide additional information on mechanisms contributing to co-occurring ASD and ID and contribute to the identification of genetic predictors of specific ASD traits. En ligne : https://doi.org/10.1002/aur.2995 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=510

Comorbid symptoms of inattention, autism, and executive cognition in youth with putative genetic risk / Anne B. ARNETT in Journal of Child Psychology and Psychiatry, 59-3 (March 2018)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 59-3 (March 2018) . - p.268-276 Titre : Comorbid symptoms of inattention, autism, and executive cognition in youth with putative genetic risk Type de document : Texte imprimé et/ou numérique Auteurs : Anne B. ARNETT, Auteur ; Brianna E. CAIRNEY, Auteur ; Arianne S. WALLACE, Auteur ; Jennifer GERDTS, Auteur ; Tychele N. TURNER, Auteur ; Evan E. EICHLER, Auteur ; Raphael BERNIER, Auteur Article en page(s) : p.268-276 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : https://doi.org/10.1111/jcpp.12815 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=339 [article] Comorbid symptoms of inattention, autism, and executive cognition in youth with putative genetic risk [Texte imprimé et/ou numérique] / Anne B. ARNETT, Auteur ; Brianna E. CAIRNEY, Auteur ; Arianne S. WALLACE, Auteur ; Jennifer GERDTS, Auteur ; Tychele N. TURNER, Auteur ; Evan E. EICHLER, Auteur ; Raphael BERNIER, Auteur . - p.268-276. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 59-3 (March 2018) . - p.268-276 Index. décimale : PER Périodiques En ligne : https://doi.org/10.1111/jcpp.12815 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=339

Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms / Eric COURCHESNE in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 22p. Titre : Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms Type de document : Texte imprimé et/ou numérique Auteurs : Eric COURCHESNE, Auteur ; Vani TALUJA, Auteur ; Sanaz NAZARI, Auteur ; Caitlin M. AAMODT, Auteur ; Karen PIERCE, Auteur ; Kuaikuai DUAN, Auteur ; Sunny STOPHAEROS, Auteur ; Linda LOPEZ, Auteur ; Cynthia Carter BARNES, Auteur ; Jaden TROXEL, Auteur ; Kathleen CAMPBELL, Auteur ; Tianyun WANG, Auteur ; Kendra HOEKZEMA, Auteur ; Evan E. EICHLER, Auteur ; Joao V. NANI, Auteur ; Wirla PONTES, Auteur ; Sandra SANCHEZ, Auteur ; Michael V. LOMBARDO, Auteur ; Janaina S. DE SOUZA, Auteur ; Mirian A. F. HAYASHI, Auteur ; Alysson R. MUOTRI, Auteur Article en page(s) : 22p. Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/pathology/physiopathology  Organoids/pathology  Male  Female  Child, Preschool  Cerebral Cortex/pathology  Social Behavior  Organ Size  Infant  Severity of Illness Index  Brain/pathology Index. décimale : PER Périodiques Résumé : BACKGROUND: Social affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with "profound" autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known. METHODS: Because ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject). In a 2021 batch, we measured BCOs from 10 ASD and 5 controls. In a 2022 batch, we  tested replicability of BCO size and growth effects by generating and measuring an independent batch of BCOs from 6 ASD and 4 control subjects. BCO size was analyzed within the context of our large, one-of-a-kind social symptom, social attention, social brain and social and language psychometric normative datasets ranging from N = 266 to N = 1902 toddlers. BCO growth rates were examined by measuring size changes between 1- and 2-months of organoid development. Neurogenesis markers at 2-months were examined at the cellular level. At the molecular level, we measured activity and expression of Ndel1; Ndel1 is a prime target for cell cycle-activated kinases; known to regulate cell cycle, proliferation, neurogenesis, and growth; and known to be involved in neuropsychiatric conditions. RESULTS: At the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences. LIMITATIONS: Larger samples of ASD toddler-derived BCO and clinical phenotypes may reveal additional ASD embryonic subtypes. CONCLUSIONS: By embryogenesis, the biological bases of two subtypes of ASD social and brain development-profound autism and mild autism-are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler's social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions. En ligne : https://dx.doi.org/10.1186/s13229-024-00602-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms [Texte imprimé et/ou numérique] / Eric COURCHESNE, Auteur ; Vani TALUJA, Auteur ; Sanaz NAZARI, Auteur ; Caitlin M. AAMODT, Auteur ; Karen PIERCE, Auteur ; Kuaikuai DUAN, Auteur ; Sunny STOPHAEROS, Auteur ; Linda LOPEZ, Auteur ; Cynthia Carter BARNES, Auteur ; Jaden TROXEL, Auteur ; Kathleen CAMPBELL, Auteur ; Tianyun WANG, Auteur ; Kendra HOEKZEMA, Auteur ; Evan E. EICHLER, Auteur ; Joao V. NANI, Auteur ; Wirla PONTES, Auteur ; Sandra SANCHEZ, Auteur ; Michael V. LOMBARDO, Auteur ; Janaina S. DE SOUZA, Auteur ; Mirian A. F. HAYASHI, Auteur ; Alysson R. MUOTRI, Auteur . - 22p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 22p. Mots-clés : Humans  Autism Spectrum Disorder/pathology/physiopathology  Organoids/pathology  Male  Female  Child, Preschool  Cerebral Cortex/pathology  Social Behavior  Organ Size  Infant  Severity of Illness Index  Brain/pathology Index. décimale : PER Périodiques Résumé : BACKGROUND: Social affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with "profound" autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known. METHODS: Because ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject). In a 2021 batch, we measured BCOs from 10 ASD and 5 controls. In a 2022 batch, we  tested replicability of BCO size and growth effects by generating and measuring an independent batch of BCOs from 6 ASD and 4 control subjects. BCO size was analyzed within the context of our large, one-of-a-kind social symptom, social attention, social brain and social and language psychometric normative datasets ranging from N = 266 to N = 1902 toddlers. BCO growth rates were examined by measuring size changes between 1- and 2-months of organoid development. Neurogenesis markers at 2-months were examined at the cellular level. At the molecular level, we measured activity and expression of Ndel1; Ndel1 is a prime target for cell cycle-activated kinases; known to regulate cell cycle, proliferation, neurogenesis, and growth; and known to be involved in neuropsychiatric conditions. RESULTS: At the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences. LIMITATIONS: Larger samples of ASD toddler-derived BCO and clinical phenotypes may reveal additional ASD embryonic subtypes. CONCLUSIONS: By embryogenesis, the biological bases of two subtypes of ASD social and brain development-profound autism and mild autism-are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler's social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions. En ligne : https://dx.doi.org/10.1186/s13229-024-00602-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

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