Clinical correlates of diagnostic certainty in children and youths with Autistic Disorder / Eya-Mist RØDGAARD in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 15p. Titre : Clinical correlates of diagnostic certainty in children and youths with Autistic Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Eya-Mist RØDGAARD, Auteur ; Borja RODRIGUEZ-HERREROS, Auteur ; Abderrahim ZERIBI, Auteur ; Kristian JENSEN, Auteur ; Valérie COURCHESNE, Auteur ; Elise DOUARD, Auteur ; David GAGNON, Auteur ; Guillaume HUGUET, Auteur ; Sebastien JACQUEMONT, Auteur ; Laurent MOTTRON, Auteur Article en page(s) : 15p. Langues : Anglais (eng) Mots-clés : Child  Humans  Adolescent  Child, Preschool  Autistic Disorder/diagnosis  Language  Autism Spectrum Disorder/diagnosis  Ados  Certainty  Diagnosis  Macrocephaly Index. décimale : PER Périodiques Résumé : BACKGROUND: Clinicians diagnosing autism rely on diagnostic criteria and instruments in combination with an implicit knowledge based on clinical expertise of the specific signs and presentations associated with the condition. This implicit knowledge influences how diagnostic criteria are interpreted, but it cannot be directly observed. Instead, insight into clinicians' understanding of autism can be gained by investigating their diagnostic certainty. Modest correlations between the certainty of an autism diagnosis and symptom load have been previously reported. Here, we investigated the associations of diagnostic certainty with specific items of the ADOS as well as other clinical features including head circumference. METHODS: Phenotypic data from the Simons Simplex Collection was used to investigate clinical correlates of diagnostic certainty in individuals diagnosed with Autistic Disorder (n = 1511, age 4 to 18 years). Participants were stratified by the ADOS module used to evaluate them. We investigated how diagnostic certainty was associated with total ADOS scores, age, and ADOS module. We calculated the odds-ratios of being diagnosed with the highest possible certainty given the presence or absence of different signs during the ADOS evaluation. Associations between diagnostic certainty and other cognitive and clinical variables were also assessed. RESULTS: In each ADOS module, some items showed a larger association with diagnostic certainty than others. Head circumference was significantly higher for individuals with the highest certainty rating across all three ADOS modules. In turn, head circumference was positively correlated with some of the ADOS items that were associated with diagnostic certainty, and was negatively correlated with verbal/nonverbal IQ ratio among those assessed with ADOS module 2. LIMITATIONS: The investigated cohort was heterogeneous, e.g. in terms of age, IQ, language level, and total ADOS score, which could impede the identification of associations that only exist in a subgroup of the population. The variability of the certainty ratings in the sample was low, limiting the power to identify potential associations with other variables. Additionally, the scoring of diagnostic certainty may vary between clinicians. CONCLUSION: Some ADOS items may better capture the signs that are most associated with clinicians' implicit knowledge of Autistic Disorder. If replicated in future studies, new diagnostic instruments with differentiated weighting of signs may be needed to better reflect this, possibly resulting in better specificity in standardized assessments. En ligne : https://dx.doi.org/10.1186/s13229-024-00592-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Clinical correlates of diagnostic certainty in children and youths with Autistic Disorder [Texte imprimé et/ou numérique] / Eya-Mist RØDGAARD, Auteur ; Borja RODRIGUEZ-HERREROS, Auteur ; Abderrahim ZERIBI, Auteur ; Kristian JENSEN, Auteur ; Valérie COURCHESNE, Auteur ; Elise DOUARD, Auteur ; David GAGNON, Auteur ; Guillaume HUGUET, Auteur ; Sebastien JACQUEMONT, Auteur ; Laurent MOTTRON, Auteur . - 15p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 15p. Mots-clés : Child  Humans  Adolescent  Child, Preschool  Autistic Disorder/diagnosis  Language  Autism Spectrum Disorder/diagnosis  Ados  Certainty  Diagnosis  Macrocephaly Index. décimale : PER Périodiques Résumé : BACKGROUND: Clinicians diagnosing autism rely on diagnostic criteria and instruments in combination with an implicit knowledge based on clinical expertise of the specific signs and presentations associated with the condition. This implicit knowledge influences how diagnostic criteria are interpreted, but it cannot be directly observed. Instead, insight into clinicians' understanding of autism can be gained by investigating their diagnostic certainty. Modest correlations between the certainty of an autism diagnosis and symptom load have been previously reported. Here, we investigated the associations of diagnostic certainty with specific items of the ADOS as well as other clinical features including head circumference. METHODS: Phenotypic data from the Simons Simplex Collection was used to investigate clinical correlates of diagnostic certainty in individuals diagnosed with Autistic Disorder (n = 1511, age 4 to 18 years). Participants were stratified by the ADOS module used to evaluate them. We investigated how diagnostic certainty was associated with total ADOS scores, age, and ADOS module. We calculated the odds-ratios of being diagnosed with the highest possible certainty given the presence or absence of different signs during the ADOS evaluation. Associations between diagnostic certainty and other cognitive and clinical variables were also assessed. RESULTS: In each ADOS module, some items showed a larger association with diagnostic certainty than others. Head circumference was significantly higher for individuals with the highest certainty rating across all three ADOS modules. In turn, head circumference was positively correlated with some of the ADOS items that were associated with diagnostic certainty, and was negatively correlated with verbal/nonverbal IQ ratio among those assessed with ADOS module 2. LIMITATIONS: The investigated cohort was heterogeneous, e.g. in terms of age, IQ, language level, and total ADOS score, which could impede the identification of associations that only exist in a subgroup of the population. The variability of the certainty ratings in the sample was low, limiting the power to identify potential associations with other variables. Additionally, the scoring of diagnostic certainty may vary between clinicians. CONCLUSION: Some ADOS items may better capture the signs that are most associated with clinicians' implicit knowledge of Autistic Disorder. If replicated in future studies, new diagnostic instruments with differentiated weighting of signs may be needed to better reflect this, possibly resulting in better specificity in standardized assessments. En ligne : https://dx.doi.org/10.1186/s13229-024-00592-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Copy-number variants in the contactin-5 gene are a potential risk factor for autism spectrum disorder / Zoe SCHMILOVICH in Research in Autism Spectrum Disorders, 99 (November)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 99 (November) . - 102055 Titre : Copy-number variants in the contactin-5 gene are a potential risk factor for autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Zoe SCHMILOVICH, Auteur ; Guillaume HUGUET, Auteur ; Qin HE, Auteur ; Amélie MUSA-JOHNSON, Auteur ; Elise DOUARD, Auteur ; Mor Absa LOUM, Auteur ; Calwing LIAO, Auteur ; Jay P. ROSS, Auteur ; Alexandre DIONNE-LAPORTE, Auteur ; Dan SPIEGELMAN, Auteur ; Martineau JEAN-LOUIS, Auteur ; Zohra SACI, Auteur ; Caroline HAYWARD, Auteur ; Tobias BANASCHEWSKI, Auteur ; Arun BOKDE, Auteur ; Sylvane DESRIVIERES, Auteur ; Herve LEMAITRE, Auteur ; Gunter SCHUMANN, Auteur ; Lan XIONG, Auteur ; Patrick A. DION, Auteur ; Sébastien JACQUEMONT, Auteur ; Boris CHAUMETTE, Auteur ; Guy A. ROULEAU, Auteur Article en page(s) : 102055 Langues : Anglais (eng) Mots-clés : CNTN5  CNV  intronic deletions  neurodevelopment  inherited Index. décimale : PER Périodiques Résumé : Background Contactin-5 (CNTN5) is a candidate risk gene for autism spectrum disorder (ASD). Previous attempts to associate CNTN5 CNVs with ASD-susceptibility were limited by insufficient statistical power. Here, we aim to clarify the putative association between CNTN5 CNVs and ASD-risk using large-scale case-control analyses. Method A CNTN5 CNV, shared by four brothers in a multiplex family with ASD, was initially identified. We calculated the prevalence and transmission of CNTN5 CNVs in cases across five ASD cohorts (n=15,784). Second, we compared the prevalence of CNTN5 CNVs in cases to their unaffected siblings (n=4,996). Third, we assessed the enrichment of CNTN5 CNVs in cases to extrafamilial controls across three cohorts (n=24,886) and the UK Biobank (n = 459,862). Finally, we evaluated the clinical impact of CNTN5 CNVs in a broad neurodevelopmental disorder cohort and the DECIPHER database. Results Most (96.7%) CNTN5 CNV deletions (0.193%) and duplications (0.03%) in cases were inherited by a parent that transmitted the variant to their affected and unaffected children at the same rate. We identified a significant enrichment of intronic CNTN5 CNV deletions in cases compared to extrafamilial controls (0.178% versus 0.019%; p-value=1.68E-05; OR:8.51; 95%CI=[2.58-44.21]). There was no difference in CNTN5 CNV enrichment between cases and individuals with NDDs. Conclusions Intronic CNTN5 CNV deletions are rare, inherited, and intermediate effect size ASD-susceptibility variants that may also confer risk for other neuropsychiatric disorders. We offer a framework to characterize candidate variants that may not be detected through small-scale approaches to implicate intermediate effect size variants in the etiology of ASD. En ligne : https://doi.org/10.1016/j.rasd.2022.102055 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=490 [article] Copy-number variants in the contactin-5 gene are a potential risk factor for autism spectrum disorder [Texte imprimé et/ou numérique] / Zoe SCHMILOVICH, Auteur ; Guillaume HUGUET, Auteur ; Qin HE, Auteur ; Amélie MUSA-JOHNSON, Auteur ; Elise DOUARD, Auteur ; Mor Absa LOUM, Auteur ; Calwing LIAO, Auteur ; Jay P. ROSS, Auteur ; Alexandre DIONNE-LAPORTE, Auteur ; Dan SPIEGELMAN, Auteur ; Martineau JEAN-LOUIS, Auteur ; Zohra SACI, Auteur ; Caroline HAYWARD, Auteur ; Tobias BANASCHEWSKI, Auteur ; Arun BOKDE, Auteur ; Sylvane DESRIVIERES, Auteur ; Herve LEMAITRE, Auteur ; Gunter SCHUMANN, Auteur ; Lan XIONG, Auteur ; Patrick A. DION, Auteur ; Sébastien JACQUEMONT, Auteur ; Boris CHAUMETTE, Auteur ; Guy A. ROULEAU, Auteur . - 102055. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 99 (November) . - 102055 Mots-clés : CNTN5  CNV  intronic deletions  neurodevelopment  inherited Index. décimale : PER Périodiques Résumé : Background Contactin-5 (CNTN5) is a candidate risk gene for autism spectrum disorder (ASD). Previous attempts to associate CNTN5 CNVs with ASD-susceptibility were limited by insufficient statistical power. Here, we aim to clarify the putative association between CNTN5 CNVs and ASD-risk using large-scale case-control analyses. Method A CNTN5 CNV, shared by four brothers in a multiplex family with ASD, was initially identified. We calculated the prevalence and transmission of CNTN5 CNVs in cases across five ASD cohorts (n=15,784). Second, we compared the prevalence of CNTN5 CNVs in cases to their unaffected siblings (n=4,996). Third, we assessed the enrichment of CNTN5 CNVs in cases to extrafamilial controls across three cohorts (n=24,886) and the UK Biobank (n = 459,862). Finally, we evaluated the clinical impact of CNTN5 CNVs in a broad neurodevelopmental disorder cohort and the DECIPHER database. Results Most (96.7%) CNTN5 CNV deletions (0.193%) and duplications (0.03%) in cases were inherited by a parent that transmitted the variant to their affected and unaffected children at the same rate. We identified a significant enrichment of intronic CNTN5 CNV deletions in cases compared to extrafamilial controls (0.178% versus 0.019%; p-value=1.68E-05; OR:8.51; 95%CI=[2.58-44.21]). There was no difference in CNTN5 CNV enrichment between cases and individuals with NDDs. Conclusions Intronic CNTN5 CNV deletions are rare, inherited, and intermediate effect size ASD-susceptibility variants that may also confer risk for other neuropsychiatric disorders. We offer a framework to characterize candidate variants that may not be detected through small-scale approaches to implicate intermediate effect size variants in the etiology of ASD. En ligne : https://doi.org/10.1016/j.rasd.2022.102055 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=490

Genetic Causes of Autism Spectrum Disorders / Guillaume HUGUET  

Public ISBD in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA Titre : Genetic Causes of Autism Spectrum Disorders Type de document : Texte imprimé et/ou numérique Auteurs : Guillaume HUGUET, Auteur ; Thomas BOURGERON, Auteur Année de publication : 2016 Importance : p.13-24 Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  CNV  Heritability  SNV  Synapse  Twin studies Index. décimale : SCI-D SCI-D - Neurosciences Résumé : In the past 30 years, twin studies have indicated a strong genetic contribution to autism spectrum disorders (ASD). The heritability of ASD is estimated to be 50%. Whereas most of the inherited part of ASD is captured by common variants, our knowledge about the genetics of ASD comes almost exclusively from identification of highly penetrant de novo mutations through candidate gene or whole exome/genome sequencing studies. Approximately 10% of patients with ASD, especially those with intellectual disability, are carriers of de novo copy number or single nucleotide variants affecting clinically relevant genes for ASD. Because of the function of these genes, it was hypothesized that abnormal synaptic plasticity and failure of neuronal/synaptic homeostasis could increase the risk of ASD. It is hoped that this knowledge will lead to better diagnosis, care, and integration of individuals with ASD. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00002-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA Genetic Causes of Autism Spectrum Disorders [Texte imprimé et/ou numérique] / Guillaume HUGUET, Auteur ; Thomas BOURGERON, Auteur . - 2016 . - p.13-24. Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  CNV  Heritability  SNV  Synapse  Twin studies Index. décimale : SCI-D SCI-D - Neurosciences Résumé : In the past 30 years, twin studies have indicated a strong genetic contribution to autism spectrum disorders (ASD). The heritability of ASD is estimated to be 50%. Whereas most of the inherited part of ASD is captured by common variants, our knowledge about the genetics of ASD comes almost exclusively from identification of highly penetrant de novo mutations through candidate gene or whole exome/genome sequencing studies. Approximately 10% of patients with ASD, especially those with intellectual disability, are carriers of de novo copy number or single nucleotide variants affecting clinically relevant genes for ASD. Because of the function of these genes, it was hypothesized that abnormal synaptic plasticity and failure of neuronal/synaptic homeostasis could increase the risk of ASD. It is hoped that this knowledge will lead to better diagnosis, care, and integration of individuals with ASD. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00002-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

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