6036 recherche sur le mot-clé 'Genetic-disorder'

22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening / Tara L. WENGER in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 27p. Titre : 22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening Type de document : texte imprimé Auteurs : Tara L. WENGER, Auteur ; Judith S. MILLER, Auteur ; Lauren M. DEPOLO, Auteur ; Ashley B. DE MARCHENA, Auteur ; Caitlin C. CLEMENTS, Auteur ; Beverly S. EMANUEL, Auteur ; Elaine H. ZACKAI, Auteur ; Donna M. MCDONALD-MCGINN, Auteur ; Robert T. SCHULTZ, Auteur Article en page(s) : 27p. Langues : Anglais (eng) Mots-clés : Abnormalities, Multiple/diagnosis  Adolescent  Adult  Analysis of Variance  Autism Spectrum Disorder/complications/diagnosis/epidemiology  Child  Child, Preschool  Chromosome Duplication  Chromosomes, Human, Pair 22  DiGeorge Syndrome/complications/diagnosis  Female  Genetic Testing  Humans  Male  Middle Aged  Social Behavior  Surveys and Questionnaires  Young Adult  22q11.2 deletion syndrome  22q11.2 duplication syndrome  Autism spectrum disorder  Developmental delay  Medical characterization  Medical screening  Neuropsychiatric functioning  Syndromic autism  Typically developing controls Index. décimale : PER Périodiques Résumé : BACKGROUND: Widespread use of microarray technology has led to increasing identification of 22q11.2 duplication syndrome (22q11.2DupS), the reciprocal syndrome of the well-characterized 22q11.2 deletion syndrome (22q11.2DS). Individuals with 22q11.2DS have elevated rates of community diagnoses of autism spectrum disorder (ASD), schizophrenia, and a range of medical problems and birth defects that necessitate extensive medical screening. Case reports of 22q11.2DupS include patients with ASD, fewer medical problems, and no schizophrenia; however, no prospective cohort study has been reported. The goals of the study were to (1) characterize the neuropsychiatric functioning of a cohort of individuals with 22q11.2DupS in comparison to large samples of typically developing controls (TDCs), ASD and 22q11.2DS; (2) estimate the prevalence of ASD in 22q11.2DupS; (3) determine whether the indications that prompted the genetic testing in 22q11.2DupS differ from 22q11.2DS and (4) determine whether comprehensive medical screening should be recommended for those diagnosed with 22q11.2DupS. METHODS: Medical characterization was done by parental questionnaire and medical chart review of individuals with 22q11.2DupS (n = 37) and 22q11.2DS (n = 101). Neuropsychiatric characterization of children with 22.11.2DupS, 22q11.2DS, TDCs, and ASD was done by parent-report questionnaires; in addition, the ASD and 22q11.2DupS groups received the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. RESULTS: Individuals with 22q11.2DupS, 22q11.2DS, and ASD had significantly impaired social interaction and adaptive behavior skills compared to TDCs. Overall, 38% of children aged 2-18 with 22q11.2DupS had community diagnoses of ASD, but fewer (14-25%) met on the basis of best clinical judgment that included ADI-R and ADOS data. Indications for genetic testing were significantly different for 22q11.2DupS and 22q11.2DS, with the deletions more commonly tested because of birth defects or medical problems, and the duplications because of developmental delay. However, when the screening protocol for 22q11.2DS was applied to the 22q11.2DupS sample, several medical problems were identified that would pose significant risk if left undetected. CONCLUSIONS: 22q11.2DupS has a high rate of ASD at 14-25%, among the highest of any genetic disorder. Prospective medical screening should be done for all patients with 22q11.2DupS, including those diagnosed due to developmental delays and ASD alone. En ligne : http://dx.doi.org/10.1186/s13229-016-0090-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] 22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening [texte imprimé] / Tara L. WENGER, Auteur ; Judith S. MILLER, Auteur ; Lauren M. DEPOLO, Auteur ; Ashley B. DE MARCHENA, Auteur ; Caitlin C. CLEMENTS, Auteur ; Beverly S. EMANUEL, Auteur ; Elaine H. ZACKAI, Auteur ; Donna M. MCDONALD-MCGINN, Auteur ; Robert T. SCHULTZ, Auteur . - 27p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 27p. Mots-clés : Abnormalities, Multiple/diagnosis  Adolescent  Adult  Analysis of Variance  Autism Spectrum Disorder/complications/diagnosis/epidemiology  Child  Child, Preschool  Chromosome Duplication  Chromosomes, Human, Pair 22  DiGeorge Syndrome/complications/diagnosis  Female  Genetic Testing  Humans  Male  Middle Aged  Social Behavior  Surveys and Questionnaires  Young Adult  22q11.2 deletion syndrome  22q11.2 duplication syndrome  Autism spectrum disorder  Developmental delay  Medical characterization  Medical screening  Neuropsychiatric functioning  Syndromic autism  Typically developing controls Index. décimale : PER Périodiques Résumé : BACKGROUND: Widespread use of microarray technology has led to increasing identification of 22q11.2 duplication syndrome (22q11.2DupS), the reciprocal syndrome of the well-characterized 22q11.2 deletion syndrome (22q11.2DS). Individuals with 22q11.2DS have elevated rates of community diagnoses of autism spectrum disorder (ASD), schizophrenia, and a range of medical problems and birth defects that necessitate extensive medical screening. Case reports of 22q11.2DupS include patients with ASD, fewer medical problems, and no schizophrenia; however, no prospective cohort study has been reported. The goals of the study were to (1) characterize the neuropsychiatric functioning of a cohort of individuals with 22q11.2DupS in comparison to large samples of typically developing controls (TDCs), ASD and 22q11.2DS; (2) estimate the prevalence of ASD in 22q11.2DupS; (3) determine whether the indications that prompted the genetic testing in 22q11.2DupS differ from 22q11.2DS and (4) determine whether comprehensive medical screening should be recommended for those diagnosed with 22q11.2DupS. METHODS: Medical characterization was done by parental questionnaire and medical chart review of individuals with 22q11.2DupS (n = 37) and 22q11.2DS (n = 101). Neuropsychiatric characterization of children with 22.11.2DupS, 22q11.2DS, TDCs, and ASD was done by parent-report questionnaires; in addition, the ASD and 22q11.2DupS groups received the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. RESULTS: Individuals with 22q11.2DupS, 22q11.2DS, and ASD had significantly impaired social interaction and adaptive behavior skills compared to TDCs. Overall, 38% of children aged 2-18 with 22q11.2DupS had community diagnoses of ASD, but fewer (14-25%) met on the basis of best clinical judgment that included ADI-R and ADOS data. Indications for genetic testing were significantly different for 22q11.2DupS and 22q11.2DS, with the deletions more commonly tested because of birth defects or medical problems, and the duplications because of developmental delay. However, when the screening protocol for 22q11.2DS was applied to the 22q11.2DupS sample, several medical problems were identified that would pose significant risk if left undetected. CONCLUSIONS: 22q11.2DupS has a high rate of ASD at 14-25%, among the highest of any genetic disorder. Prospective medical screening should be done for all patients with 22q11.2DupS, including those diagnosed due to developmental delays and ASD alone. En ligne : http://dx.doi.org/10.1186/s13229-016-0090-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Absence of preference for social novelty and increased grooming in integrin β3 knockout mice: Initial studies and future directions / Michelle D. CARTER in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.57-67 Titre : Absence of preference for social novelty and increased grooming in integrin β3 knockout mice: Initial studies and future directions Type de document : texte imprimé Auteurs : Michelle D. CARTER, Auteur ; Charisma R. SHAH, Auteur ; Christopher L. MULLER, Auteur ; Jacqueline N. CRAWLEY, Auteur ; Ana M.D. CARNEIRO, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur Année de publication : 2011 Article en page(s) : p.57-67 Langues : Anglais (eng) Mots-clés : autism  genetic  integrin  cell adhesion  serotonin  social memory  grooming  obsessive–compulsive disorder Index. décimale : PER Périodiques Résumé : Elevated whole blood serotonin 5-HT, or hyperserotonemia, is a common biomarker in autism spectrum disorder (ASD). The integrin β3 receptor subunit gene (ITGB3) is a quantitative trait locus for whole blood 5-HT levels. Recent work shows that integrin β3 interacts with the serotonin transporter (SERT) in both platelets and in the midbrain. Furthermore, multiple studies have now reported gene–gene interaction between the integrin β3 and SERT genes in association with ASD. Given the lack of previous data on the impact of integrin β3 on brain or behavioral phenotypes, we sought to compare mice with decreased or absent expression of the integrin β3 receptor subunit (Itgb3 + / − and −/ −) with wildtype littermate controls in behavioral tasks relevant to ASD. These mice did not show deficits in activity level in the open field or anxiety-like behavior on the elevated plus maze, two potential confounds in the evaluation of mouse social behavior. In the three-chamber social test, mice lacking integrin β3 were shown to have normal sociability but did not show a preference for social novelty. Importantly, the absence of integrin β3 did not impair olfaction or the ability to recall familiar social odors. Additionally, mice lacking integrin β3 showed increased grooming behavior in novel environments. These preliminary studies reveal altered social and repetitive behavior in these mice, which suggests that the integrin β3 subunit may be involved in brain systems relevant to ASD. Further work is needed to fully characterize these behavioral changes and the underlying brain mechanisms. En ligne : http://dx.doi.org/10.1002/aur.180 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] Absence of preference for social novelty and increased grooming in integrin β3 knockout mice: Initial studies and future directions [texte imprimé] / Michelle D. CARTER, Auteur ; Charisma R. SHAH, Auteur ; Christopher L. MULLER, Auteur ; Jacqueline N. CRAWLEY, Auteur ; Ana M.D. CARNEIRO, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur . - 2011 . - p.57-67. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.57-67 Mots-clés : autism  genetic  integrin  cell adhesion  serotonin  social memory  grooming  obsessive–compulsive disorder Index. décimale : PER Périodiques Résumé : Elevated whole blood serotonin 5-HT, or hyperserotonemia, is a common biomarker in autism spectrum disorder (ASD). The integrin β3 receptor subunit gene (ITGB3) is a quantitative trait locus for whole blood 5-HT levels. Recent work shows that integrin β3 interacts with the serotonin transporter (SERT) in both platelets and in the midbrain. Furthermore, multiple studies have now reported gene–gene interaction between the integrin β3 and SERT genes in association with ASD. Given the lack of previous data on the impact of integrin β3 on brain or behavioral phenotypes, we sought to compare mice with decreased or absent expression of the integrin β3 receptor subunit (Itgb3 + / − and −/ −) with wildtype littermate controls in behavioral tasks relevant to ASD. These mice did not show deficits in activity level in the open field or anxiety-like behavior on the elevated plus maze, two potential confounds in the evaluation of mouse social behavior. In the three-chamber social test, mice lacking integrin β3 were shown to have normal sociability but did not show a preference for social novelty. Importantly, the absence of integrin β3 did not impair olfaction or the ability to recall familiar social odors. Additionally, mice lacking integrin β3 showed increased grooming behavior in novel environments. These preliminary studies reveal altered social and repetitive behavior in these mice, which suggests that the integrin β3 subunit may be involved in brain systems relevant to ASD. Further work is needed to fully characterize these behavioral changes and the underlying brain mechanisms. En ligne : http://dx.doi.org/10.1002/aur.180 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118

An atlas of genetic correlations between gestational age and common psychiatric disorders / Yao YAO in Autism Research, 15-6 (June 2022)  

Public ISBD [article]  inAutism Research > 15-6 (June 2022) . - p.1008-1017 Titre : An atlas of genetic correlations between gestational age and common psychiatric disorders Type de document : texte imprimé Auteurs : Yao YAO, Auteur ; Chun'e LI, Auteur ; Peilin MENG, Auteur ; Bolun CHENG, Auteur ; Shiqiang CHENG, Auteur ; Li LIU, Auteur ; Xuena YANG, Auteur ; Yumeng JIA, Auteur ; Yan WEN, Auteur ; Feng ZHANG, Auteur Article en page(s) : p.1008-1017 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  Autism Spectrum Disorder/genetics  Depressive Disorder, Major/genetics  Female  Genetic Predisposition to Disease  Genome-Wide Association Study  Gestational Age  Humans  Infant, Newborn  Mendelian Randomization Analysis  Premature Birth/genetics  Proteomics  genetic correlation  linkage disequilibrium score regression  psychiatric disorders Index. décimale : PER Périodiques Résumé : We aim to systematically explore the potential genetic correlations between five major psychiatric disorders and gestational ages. Genome-wide association study (GWAS) summary datasets of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) in discovery were downloaded from the Psychiatric GWAS Consortium (PGC) website. Suggestive (Raw p?< 0.05) genetic associations in the discovery phrase were further replicated in independent GWASs which downloaded from PGC, the FinnGen study or Integrative Psychiatric Research (iPSYCH) website. GWASs of gestational duration, preterm and post-term birth were derived from previous studies of infants from the Early Growth Genetics (EGG) Consortium, the iPSYCH study, and the Genomic and Proteomic Network for Preterm Birth Research (GPN). We calculated genetic correlations using linkage disequilibrium score (LDSC) regression. Mendelian randomization (MR) analyses were performed to investigate the causal effects. We identified four suggestive genetic correlations between psychiatric disorders and gestational age factors in discovery LDSC and two replicated in a confirmation LDSC: gestational duration and ADHD (r(g) = -0.1405, FDR p = 0.0406), post-term birth and SCZ (r(g) = -0.2003, FDR p = 0.0042). We also observed causal effect of post-term birth on SCZ by MR (P(Weighted median) = 0.037, P(Inverse variance weighted) = 0.007). Our analysis suggested no significant evidence of horizontal pleiotropy and heterogeneity. This study showed the genetic correlation evidences between gestational age phenotypes and psychiatric disorders, providing novel clues for understanding the pathogenic factors of common psychiatric disorders. LAY SUMMARY: Whereas gestational age factors were reported to be associated with psychiatric disorders, the genetic relationship and causality remain to be revealed. The present study reported the first large-scale genetic correlations investigation of the associations between gestational age phenotypes and psychiatric disorders. Results indicate causal relationships between post-term birth and schizophrenia (SCZ), as well as suggestive genetic correlations between gestational duration and attention deficit/hyperactivity disorder (ADHD). This study provided novel clues for understanding the pathogenic factors of common psychiatric disorders. En ligne : http://dx.doi.org/10.1002/aur.2719 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476 [article] An atlas of genetic correlations between gestational age and common psychiatric disorders [texte imprimé] / Yao YAO, Auteur ; Chun'e LI, Auteur ; Peilin MENG, Auteur ; Bolun CHENG, Auteur ; Shiqiang CHENG, Auteur ; Li LIU, Auteur ; Xuena YANG, Auteur ; Yumeng JIA, Auteur ; Yan WEN, Auteur ; Feng ZHANG, Auteur . - p.1008-1017. Langues : Anglais (eng) in Autism Research > 15-6 (June 2022) . - p.1008-1017 Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  Autism Spectrum Disorder/genetics  Depressive Disorder, Major/genetics  Female  Genetic Predisposition to Disease  Genome-Wide Association Study  Gestational Age  Humans  Infant, Newborn  Mendelian Randomization Analysis  Premature Birth/genetics  Proteomics  genetic correlation  linkage disequilibrium score regression  psychiatric disorders Index. décimale : PER Périodiques Résumé : We aim to systematically explore the potential genetic correlations between five major psychiatric disorders and gestational ages. Genome-wide association study (GWAS) summary datasets of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) in discovery were downloaded from the Psychiatric GWAS Consortium (PGC) website. Suggestive (Raw p?< 0.05) genetic associations in the discovery phrase were further replicated in independent GWASs which downloaded from PGC, the FinnGen study or Integrative Psychiatric Research (iPSYCH) website. GWASs of gestational duration, preterm and post-term birth were derived from previous studies of infants from the Early Growth Genetics (EGG) Consortium, the iPSYCH study, and the Genomic and Proteomic Network for Preterm Birth Research (GPN). We calculated genetic correlations using linkage disequilibrium score (LDSC) regression. Mendelian randomization (MR) analyses were performed to investigate the causal effects. We identified four suggestive genetic correlations between psychiatric disorders and gestational age factors in discovery LDSC and two replicated in a confirmation LDSC: gestational duration and ADHD (r(g) = -0.1405, FDR p = 0.0406), post-term birth and SCZ (r(g) = -0.2003, FDR p = 0.0042). We also observed causal effect of post-term birth on SCZ by MR (P(Weighted median) = 0.037, P(Inverse variance weighted) = 0.007). Our analysis suggested no significant evidence of horizontal pleiotropy and heterogeneity. This study showed the genetic correlation evidences between gestational age phenotypes and psychiatric disorders, providing novel clues for understanding the pathogenic factors of common psychiatric disorders. LAY SUMMARY: Whereas gestational age factors were reported to be associated with psychiatric disorders, the genetic relationship and causality remain to be revealed. The present study reported the first large-scale genetic correlations investigation of the associations between gestational age phenotypes and psychiatric disorders. Results indicate causal relationships between post-term birth and schizophrenia (SCZ), as well as suggestive genetic correlations between gestational duration and attention deficit/hyperactivity disorder (ADHD). This study provided novel clues for understanding the pathogenic factors of common psychiatric disorders. En ligne : http://dx.doi.org/10.1002/aur.2719 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476

An integrated clinical approach to children at genetic risk for neurodevelopmental and psychiatric conditions: interdisciplinary collaboration and research infrastructure / Jane SUMMERS in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : An integrated clinical approach to children at genetic risk for neurodevelopmental and psychiatric conditions: interdisciplinary collaboration and research infrastructure Type de document : texte imprimé Auteurs : Jane SUMMERS, Auteur ; Danielle BARIBEAU, Auteur ; Polina PERLMAN, Auteur ; Ny HOANG, Auteur ; Sunny CUI, Auteur ; Aneta KRAKOWSKI, Auteur ; Patricia AMBROZEWICZ, Auteur ; Ariel HO, Auteur ; Thanuja SELVANAYAGAM, Auteur ; Kinga A. SÁNDOR-BAJUSZ, Auteur ; Katrina PALAD, Auteur ; Nishi PATEL, Auteur ; Sarah MCGAUGHEY, Auteur ; Louise GALLAGHER, Auteur ; Stephen W. SCHERER, Auteur ; Peter SZATMARI, Auteur ; Jacob VORSTMAN, Auteur Langues : Anglais (eng) Mots-clés : Humans  Child  Neurodevelopmental Disorders/genetics  Female  Male  Mental Disorders/genetics  Genetic Predisposition to Disease  Adolescent  Genetic disorder  Genetics  Interdisciplinary clinic  Mental health  Neurodevelopmental disorder  Psychiatry  Psychology  Research framework  speaker fees for Henry Stewart Talks Ltd. S.W.S. is on the Scientific Advisory  Committee of Population Bio, Deep Genomics, and serves as a Highly Cited Academic  Advisor for King Abdulaziz University. Intellectual property from aspects of his  research held at The Hospital for Sick Children are licensed to Athena  Diagnostics and Population Bio. D.B. has received research funding from MapLight  therapeutics. These relationships did not influence content of this manuscript  but are disclosed for potential future considerations. Index. décimale : PER Périodiques Résumé : BACKGROUND: A sizeable proportion of pathogenic genetic variants identified in young children tested for congenital differences are associated with neurodevelopmental psychiatric disorders (NPD). In this growing group, a genetic diagnosis often precedes the emergence of diagnosable developmental concerns. Here, we describe DAGSY (Developmental Assessment of Genetically Susceptible Youth), a novel interdisciplinary 'genetic-diagnosis-first' clinic integrating psychiatric, psychological and genetic expertise, and report our first observations and feedback from families and referring clinicians. METHODS: We retrieved data on referral sources and indications, genetic and NPD diagnoses and recommendations for children seen at DAGSY between 2018 and 2022. Through a survey, we obtained feedback from twenty families and eleven referring clinicians. RESULTS: 159 children (mean age 10.2 years, 57.2% males) completed an interdisciplinary (psychiatry, psychology, genetic counselling) DAGSY assessment during this period. Of these, 69.8% had a pathogenic microdeletion or microduplication, 21.5% a sequence-level variant, 4.4% a chromosomal disorder, and 4.4% a variant of unknown significance with emerging evidence of pathogenicity. One in four children did not have a prior NPD diagnosis, and referral to DAGSY was motivated by their genetic vulnerability alone. Following assessment, 76.7% received at least one new NPD diagnosis, most frequently intellectual disability (24.5%), anxiety (20.7%), autism spectrum (18.9%) and specific learning (16.4%) disorder. Both families and clinicians responding to our survey expressed satisfaction, but also highlighted some areas for potential improvement. CONCLUSIONS: DAGSY addresses an unmet clinical need for children identified with genetic variants that confer increased vulnerability for NPD and provides a crucial platform for research in this area. DAGSY can serve as a model for interdisciplinary clinics integrating child psychiatry, psychology and genetics, addressing both clinical and research needs for this emerging population. En ligne : https://dx.doi.org/10.1186/s11689-024-09552-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] An integrated clinical approach to children at genetic risk for neurodevelopmental and psychiatric conditions: interdisciplinary collaboration and research infrastructure [texte imprimé] / Jane SUMMERS, Auteur ; Danielle BARIBEAU, Auteur ; Polina PERLMAN, Auteur ; Ny HOANG, Auteur ; Sunny CUI, Auteur ; Aneta KRAKOWSKI, Auteur ; Patricia AMBROZEWICZ, Auteur ; Ariel HO, Auteur ; Thanuja SELVANAYAGAM, Auteur ; Kinga A. SÁNDOR-BAJUSZ, Auteur ; Katrina PALAD, Auteur ; Nishi PATEL, Auteur ; Sarah MCGAUGHEY, Auteur ; Louise GALLAGHER, Auteur ; Stephen W. SCHERER, Auteur ; Peter SZATMARI, Auteur ; Jacob VORSTMAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Child  Neurodevelopmental Disorders/genetics  Female  Male  Mental Disorders/genetics  Genetic Predisposition to Disease  Adolescent  Genetic disorder  Genetics  Interdisciplinary clinic  Mental health  Neurodevelopmental disorder  Psychiatry  Psychology  Research framework  speaker fees for Henry Stewart Talks Ltd. S.W.S. is on the Scientific Advisory  Committee of Population Bio, Deep Genomics, and serves as a Highly Cited Academic  Advisor for King Abdulaziz University. Intellectual property from aspects of his  research held at The Hospital for Sick Children are licensed to Athena  Diagnostics and Population Bio. D.B. has received research funding from MapLight  therapeutics. These relationships did not influence content of this manuscript  but are disclosed for potential future considerations. Index. décimale : PER Périodiques Résumé : BACKGROUND: A sizeable proportion of pathogenic genetic variants identified in young children tested for congenital differences are associated with neurodevelopmental psychiatric disorders (NPD). In this growing group, a genetic diagnosis often precedes the emergence of diagnosable developmental concerns. Here, we describe DAGSY (Developmental Assessment of Genetically Susceptible Youth), a novel interdisciplinary 'genetic-diagnosis-first' clinic integrating psychiatric, psychological and genetic expertise, and report our first observations and feedback from families and referring clinicians. METHODS: We retrieved data on referral sources and indications, genetic and NPD diagnoses and recommendations for children seen at DAGSY between 2018 and 2022. Through a survey, we obtained feedback from twenty families and eleven referring clinicians. RESULTS: 159 children (mean age 10.2 years, 57.2% males) completed an interdisciplinary (psychiatry, psychology, genetic counselling) DAGSY assessment during this period. Of these, 69.8% had a pathogenic microdeletion or microduplication, 21.5% a sequence-level variant, 4.4% a chromosomal disorder, and 4.4% a variant of unknown significance with emerging evidence of pathogenicity. One in four children did not have a prior NPD diagnosis, and referral to DAGSY was motivated by their genetic vulnerability alone. Following assessment, 76.7% received at least one new NPD diagnosis, most frequently intellectual disability (24.5%), anxiety (20.7%), autism spectrum (18.9%) and specific learning (16.4%) disorder. Both families and clinicians responding to our survey expressed satisfaction, but also highlighted some areas for potential improvement. CONCLUSIONS: DAGSY addresses an unmet clinical need for children identified with genetic variants that confer increased vulnerability for NPD and provides a crucial platform for research in this area. DAGSY can serve as a model for interdisciplinary clinics integrating child psychiatry, psychology and genetics, addressing both clinical and research needs for this emerging population. En ligne : https://dx.doi.org/10.1186/s11689-024-09552-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Association between rare, genetic variants linked to autism and ultrasonography fetal anomalies in children with autism spectrum disorder / Ohad REGEV in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Association between rare, genetic variants linked to autism and ultrasonography fetal anomalies in children with autism spectrum disorder Type de document : texte imprimé Auteurs : Ohad REGEV, Auteur ; Apurba SHIL, Auteur ; Tal BRONSHTEIN, Auteur ; Amnon HADAR, Auteur ; Gal MEIRI, Auteur ; Dikla ZIGDON, Auteur ; Analya MICHAELOVSKI, Auteur ; Reli HERSHKOVITZ, Auteur ; Idan MENASHE, Auteur Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/genetics/diagnostic imaging  Female  Male  Ultrasonography, Prenatal  Child  Exome Sequencing  Pregnancy  Cross-Sectional Studies  Child, Preschool  Genetic Variation  Genetic Predisposition to Disease  Autism spectrum disorder  Congenital anomalies  Fetal development  Genetic mutations  Prenatal ultrasound  Ultrasonography fetal anomalies  Whole-exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent evidence suggests that certain fetal anomalies detected upon prenatal ultrasound screenings are associated with autism spectrum disorder (ASD). In this cross-sectional study, we aimed to identify genetic variants associated with fetal ultrasound anomalies (UFAs) in children with ASD. METHODS: The study included all children with ASD who are registered in the database of the Azrieli National Center of Autism and Neurodevelopment and for whom both prenatal ultrasound and whole exome sequencing (WES) data were available. We applied our in-house integrative bioinformatics pipeline, AutScore, to these WES data to prioritize rare, gene-disrupting variants (GDVs) probably contributing to ASD susceptibily. Univariate statistics and multivariable regression were used to assess the associations between UFAs and GDVs identified in these children. RESULTS: The study sample comprised 126 children, of whom 43 (34.1%) had at least one UFA detected in the prenatal ultrasound scan. A total of 87 candidate ASD genetic variants were detected in 60 children, with 24 (40%) children carrying multiple variants. Children with UFAs were more likely to have loss-of-function (LoF) mutations (aOR = 2.55, 95%CI: 1.13-5.80). This association was particularly noticeable when children with structural anomalies or children with UFAs in their head and brain scans were compared to children without UFAs (any mutation: aOR = 8.28, 95%CI: 2.29-30.01; LoF: aOR = 5.72, 95%CI: 2.08-15.71 and any mutation: aOR = 6.39, 95%CI: 1.34-30.47; LoF: aOR = 4.50, 95%CI: 1.32-15.35, respectively). GDVs associated with UFAs were enriched in genes highly expressed across all tissues (aOR = 2.76, 95%CI: 1.14-6.68). There was a weak, but significant, correlation between the number of mutations and the number of abnormalities detected in the same children (r = 0.21, P = 0.016). CONCLUSIONS: The results provide valuable insights into the potential genetic basis of prenatal organogenesis abnormalities associated with ASD and shed light on the complex interplay between genetic factors and fetal development. En ligne : https://dx.doi.org/10.1186/s11689-024-09573-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Association between rare, genetic variants linked to autism and ultrasonography fetal anomalies in children with autism spectrum disorder [texte imprimé] / Ohad REGEV, Auteur ; Apurba SHIL, Auteur ; Tal BRONSHTEIN, Auteur ; Amnon HADAR, Auteur ; Gal MEIRI, Auteur ; Dikla ZIGDON, Auteur ; Analya MICHAELOVSKI, Auteur ; Reli HERSHKOVITZ, Auteur ; Idan MENASHE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Autism Spectrum Disorder/genetics/diagnostic imaging  Female  Male  Ultrasonography, Prenatal  Child  Exome Sequencing  Pregnancy  Cross-Sectional Studies  Child, Preschool  Genetic Variation  Genetic Predisposition to Disease  Autism spectrum disorder  Congenital anomalies  Fetal development  Genetic mutations  Prenatal ultrasound  Ultrasonography fetal anomalies  Whole-exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent evidence suggests that certain fetal anomalies detected upon prenatal ultrasound screenings are associated with autism spectrum disorder (ASD). In this cross-sectional study, we aimed to identify genetic variants associated with fetal ultrasound anomalies (UFAs) in children with ASD. METHODS: The study included all children with ASD who are registered in the database of the Azrieli National Center of Autism and Neurodevelopment and for whom both prenatal ultrasound and whole exome sequencing (WES) data were available. We applied our in-house integrative bioinformatics pipeline, AutScore, to these WES data to prioritize rare, gene-disrupting variants (GDVs) probably contributing to ASD susceptibily. Univariate statistics and multivariable regression were used to assess the associations between UFAs and GDVs identified in these children. RESULTS: The study sample comprised 126 children, of whom 43 (34.1%) had at least one UFA detected in the prenatal ultrasound scan. A total of 87 candidate ASD genetic variants were detected in 60 children, with 24 (40%) children carrying multiple variants. Children with UFAs were more likely to have loss-of-function (LoF) mutations (aOR = 2.55, 95%CI: 1.13-5.80). This association was particularly noticeable when children with structural anomalies or children with UFAs in their head and brain scans were compared to children without UFAs (any mutation: aOR = 8.28, 95%CI: 2.29-30.01; LoF: aOR = 5.72, 95%CI: 2.08-15.71 and any mutation: aOR = 6.39, 95%CI: 1.34-30.47; LoF: aOR = 4.50, 95%CI: 1.32-15.35, respectively). GDVs associated with UFAs were enriched in genes highly expressed across all tissues (aOR = 2.76, 95%CI: 1.14-6.68). There was a weak, but significant, correlation between the number of mutations and the number of abnormalities detected in the same children (r = 0.21, P = 0.016). CONCLUSIONS: The results provide valuable insights into the potential genetic basis of prenatal organogenesis abnormalities associated with ASD and shed light on the complex interplay between genetic factors and fetal development. En ligne : https://dx.doi.org/10.1186/s11689-024-09573-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

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