De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures / Beryl ROYER-BERTRAND in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 69 p. Titre : De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures Type de document : texte imprimé Auteurs : Beryl ROYER-BERTRAND, Auteur ; Marine JEQUIER GYGAX, Auteur ; Katarina CISAROVA, Auteur ; Jill A. ROSENFELD, Auteur ; Jennifer A. BASSETTI, Auteur ; Oana MOLDOVAN, Auteur ; Emily O'HEIR, Auteur ; Lindsay C. BURRAGE, Auteur ; Jake ALLEN, Auteur ; Lisa T. EMRICK, Auteur ; Emma EASTMAN, Auteur ; Camille KUMPS, Auteur ; Safdar ABBAS, Auteur ; Geraldine VAN WINCKEL, Auteur ; Nadia CHABANE, Auteur ; Elaine H. ZACKAI, Auteur ; Sebastien LEBON, Auteur ; Beth KEENA, Auteur ; Elizabeth J. BHOJ, Auteur ; Muhammad UMAIR, Auteur ; Dong LI, Auteur ; Kirsten A. DONALD, Auteur ; Andrea SUPERTI-FURGA, Auteur Article en page(s) : 69 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Cacna1e  Developmental regression  Epilepsy  Exome sequencing  Global developmental delay  Intellectual disability  Neurodevelopmental disorders  Seizures  Topiramate  receives revenue from clinical genetic testing completed at Baylor Genetics  Laboratories. Index. décimale : PER Périodiques Résumé : BACKGROUND: De novo variants in the voltage-gated calcium channel subunit α1 E gene (CACNA1E) have been described as causative of epileptic encephalopathy with contractures, macrocephaly and dyskinesias. METHODS: Following the observation of an index patient with developmental delay and autism spectrum disorder (ASD) without seizures who had a de novo deleterious CACNA1E variant, we screened GeneMatcher for other individuals with CACNA1E variants and neurodevelopmental phenotypes without epilepsy. The spectrum of pathogenic CACNA1E variants was compared to the mutational landscape of variants in the gnomAD control population database. RESULTS: We identified seven unrelated individuals with intellectual disability, developmental regression and ASD-like behavioral profile, and notably without epilepsy, who had de novo heterozygous putatively pathogenic variants in CACNA1E. Age of onset of clinical manifestation, presence or absence of regression and degree of severity were variable, and no clear-cut genotype-phenotype association could be recognized. The analysis of disease-associated variants and their comparison to benign variants from the control population allowed for the identification of regions in the CACNA1E protein that seem to be intolerant to substitutions and thus more likely to harbor pathogenic variants. As in a few reported cases with CACNA1E variants and epilepsy, one patient showed a positive clinical behavioral response to topiramate, a specific calcium channel modulator. LIMITATIONS: The significance of our study is limited by the absence of functional experiments of the effect of identified variants, the small sample size and the lack of systematic ASD assessment in all participants. Moreover, topiramate was given to one patient only and for a short period of time. CONCLUSIONS: Our results indicate that CACNA1E variants may result in neurodevelopmental disorders without epilepsy and expand the mutational and phenotypic spectrum of this gene. CACNA1E deserves to be included in gene panels for non-specific developmental disorders, including ASD, and not limited to patients with seizures, to improve diagnostic recognition and explore the possible efficacy of topiramate. En ligne : http://dx.doi.org/10.1186/s13229-021-00473-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures [texte imprimé] / Beryl ROYER-BERTRAND, Auteur ; Marine JEQUIER GYGAX, Auteur ; Katarina CISAROVA, Auteur ; Jill A. ROSENFELD, Auteur ; Jennifer A. BASSETTI, Auteur ; Oana MOLDOVAN, Auteur ; Emily O'HEIR, Auteur ; Lindsay C. BURRAGE, Auteur ; Jake ALLEN, Auteur ; Lisa T. EMRICK, Auteur ; Emma EASTMAN, Auteur ; Camille KUMPS, Auteur ; Safdar ABBAS, Auteur ; Geraldine VAN WINCKEL, Auteur ; Nadia CHABANE, Auteur ; Elaine H. ZACKAI, Auteur ; Sebastien LEBON, Auteur ; Beth KEENA, Auteur ; Elizabeth J. BHOJ, Auteur ; Muhammad UMAIR, Auteur ; Dong LI, Auteur ; Kirsten A. DONALD, Auteur ; Andrea SUPERTI-FURGA, Auteur . - 69 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 69 p. Mots-clés : Autism spectrum disorder  Cacna1e  Developmental regression  Epilepsy  Exome sequencing  Global developmental delay  Intellectual disability  Neurodevelopmental disorders  Seizures  Topiramate  receives revenue from clinical genetic testing completed at Baylor Genetics  Laboratories. Index. décimale : PER Périodiques Résumé : BACKGROUND: De novo variants in the voltage-gated calcium channel subunit α1 E gene (CACNA1E) have been described as causative of epileptic encephalopathy with contractures, macrocephaly and dyskinesias. METHODS: Following the observation of an index patient with developmental delay and autism spectrum disorder (ASD) without seizures who had a de novo deleterious CACNA1E variant, we screened GeneMatcher for other individuals with CACNA1E variants and neurodevelopmental phenotypes without epilepsy. The spectrum of pathogenic CACNA1E variants was compared to the mutational landscape of variants in the gnomAD control population database. RESULTS: We identified seven unrelated individuals with intellectual disability, developmental regression and ASD-like behavioral profile, and notably without epilepsy, who had de novo heterozygous putatively pathogenic variants in CACNA1E. Age of onset of clinical manifestation, presence or absence of regression and degree of severity were variable, and no clear-cut genotype-phenotype association could be recognized. The analysis of disease-associated variants and their comparison to benign variants from the control population allowed for the identification of regions in the CACNA1E protein that seem to be intolerant to substitutions and thus more likely to harbor pathogenic variants. As in a few reported cases with CACNA1E variants and epilepsy, one patient showed a positive clinical behavioral response to topiramate, a specific calcium channel modulator. LIMITATIONS: The significance of our study is limited by the absence of functional experiments of the effect of identified variants, the small sample size and the lack of systematic ASD assessment in all participants. Moreover, topiramate was given to one patient only and for a short period of time. CONCLUSIONS: Our results indicate that CACNA1E variants may result in neurodevelopmental disorders without epilepsy and expand the mutational and phenotypic spectrum of this gene. CACNA1E deserves to be included in gene panels for non-specific developmental disorders, including ASD, and not limited to patients with seizures, to improve diagnostic recognition and explore the possible efficacy of topiramate. En ligne : http://dx.doi.org/10.1186/s13229-021-00473-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Sex differences in sensory processing in children with autism spectrum disorder / Joana Maria Almeida OSORIO in Autism Research, 14-11 (November 2021)  

Public ISBD [article]  inAutism Research > 14-11 (November 2021) . - p.2412-2423 Titre : Sex differences in sensory processing in children with autism spectrum disorder Type de document : texte imprimé Auteurs : Joana Maria Almeida OSORIO, Auteur ; Borja RODRIGUEZ-HERREROS, Auteur ; Sonia RICHETIN, Auteur ; Vincent JUNOD, Auteur ; David ROMASCANO, Auteur ; Valérie PITTET, Auteur ; Nadia CHABANE, Auteur ; Marine JEQUIER GYGAX, Auteur ; Anne Manuela MAILLARD, Auteur Article en page(s) : p.2412-2423 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/complications  Autistic Disorder  Child  Child, Preschool  Cognition  Female  Humans  Male  Perception  Sex Characteristics  autism spectrum disorder (ASD)  child development  sensory processing  sensory processing measure (SPM)  sex differences Index. décimale : PER Périodiques Résumé : Despite the high prevalence of sensory processing difficulties in children with autism spectrum disorder (ASD), little research has focused on the sex differences in sensory processing. Furthermore, there is a lack of knowledge on the female-specific symptoms of ASD, contributing to later referral, diagnosis and intervention. In this study, we examined the sex differences in sensory processing symptoms in large cohorts of ASD children (N = 168; 26 females, 142 males) and typically developing (TD) children (N = 439; 209 females, 230 males). For this, we translated the sensory processing measure (SPM) and SPM - Preschool (SPM-P) Home Forms to French. The SPM/SPM-P are parent/caregiver questionnaires that assess typical behavioral responses to sensory stimuli. Overall, our results showed that the magnitude of the differences in sensory processing between males and females is larger in ASD children relative to TD children, with females showing more severe symptoms in Hearing, as well as Balance and Motion subscales. Additionally, linear discriminant analysis showed that the SPM/SPM-P are good at discriminating TD children from ASD, children with higher accuracy rates for females than for males. These findings are discussed in light of the heterogeneity of sensory processing difficulties present in ASD. Overall, our results suggest that there seem to be female-specific profiles in sensory processing difficulties in ASD. Implications of findings concerning sex differences in sensory processing and their potential for improving identification and diagnosis of ASD females are discussed. LAY SUMMARY: The present study examined sex differences in behavioral responses to sensory stimuli in children with autism spectrum disorder (ASD), and typically developing (TD) children. While there is a small trend for TD males to show more sensory processing atypicalities, female ASD children show significantly more atypical responses compared to their male counterparts. This has important implications for characterizing female autism profiles, and ultimately improving the chance for earlier detection, diagnosis and treatment. En ligne : http://dx.doi.org/10.1002/aur.2580 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450 [article] Sex differences in sensory processing in children with autism spectrum disorder [texte imprimé] / Joana Maria Almeida OSORIO, Auteur ; Borja RODRIGUEZ-HERREROS, Auteur ; Sonia RICHETIN, Auteur ; Vincent JUNOD, Auteur ; David ROMASCANO, Auteur ; Valérie PITTET, Auteur ; Nadia CHABANE, Auteur ; Marine JEQUIER GYGAX, Auteur ; Anne Manuela MAILLARD, Auteur . - p.2412-2423. Langues : Anglais (eng) in Autism Research > 14-11 (November 2021) . - p.2412-2423 Mots-clés : Autism Spectrum Disorder/complications  Autistic Disorder  Child  Child, Preschool  Cognition  Female  Humans  Male  Perception  Sex Characteristics  autism spectrum disorder (ASD)  child development  sensory processing  sensory processing measure (SPM)  sex differences Index. décimale : PER Périodiques Résumé : Despite the high prevalence of sensory processing difficulties in children with autism spectrum disorder (ASD), little research has focused on the sex differences in sensory processing. Furthermore, there is a lack of knowledge on the female-specific symptoms of ASD, contributing to later referral, diagnosis and intervention. In this study, we examined the sex differences in sensory processing symptoms in large cohorts of ASD children (N = 168; 26 females, 142 males) and typically developing (TD) children (N = 439; 209 females, 230 males). For this, we translated the sensory processing measure (SPM) and SPM - Preschool (SPM-P) Home Forms to French. The SPM/SPM-P are parent/caregiver questionnaires that assess typical behavioral responses to sensory stimuli. Overall, our results showed that the magnitude of the differences in sensory processing between males and females is larger in ASD children relative to TD children, with females showing more severe symptoms in Hearing, as well as Balance and Motion subscales. Additionally, linear discriminant analysis showed that the SPM/SPM-P are good at discriminating TD children from ASD, children with higher accuracy rates for females than for males. These findings are discussed in light of the heterogeneity of sensory processing difficulties present in ASD. Overall, our results suggest that there seem to be female-specific profiles in sensory processing difficulties in ASD. Implications of findings concerning sex differences in sensory processing and their potential for improving identification and diagnosis of ASD females are discussed. LAY SUMMARY: The present study examined sex differences in behavioral responses to sensory stimuli in children with autism spectrum disorder (ASD), and typically developing (TD) children. While there is a small trend for TD males to show more sensory processing atypicalities, female ASD children show significantly more atypical responses compared to their male counterparts. This has important implications for characterizing female autism profiles, and ultimately improving the chance for earlier detection, diagnosis and treatment. En ligne : http://dx.doi.org/10.1002/aur.2580 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450

Touch and olfaction/taste differentiate children carrying a 16p11.2 deletion from children with ASD / Joana Maria Almeida OSORIO in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 8p. Titre : Touch and olfaction/taste differentiate children carrying a 16p11.2 deletion from children with ASD Type de document : texte imprimé Auteurs : Joana Maria Almeida OSORIO, Auteur ; Borja RODRIGUEZ-HERREROS, Auteur ; David ROMASCANO, Auteur ; Vincent JUNOD, Auteur ; Aline HABEGGER, Auteur ; Aurélie PAIN, Auteur ; Sonia RICHETIN, Auteur ; Paola YU, Auteur ; Bertrand ISIDOR, Auteur ; Lionel VAN MALDERGEM, Auteur ; Linda PONS, Auteur ; Sabine MANIFICAT, Auteur ; Nadia CHABANE, Auteur ; Marine JEQUIER GYGAX, Auteur ; Anne Manuela MAILLARD, Auteur Article en page(s) : 8p. Langues : Anglais (eng) Mots-clés : 16p11.2 deletion  Autism spectrum disorder (ASD)  Children  Copy number variants (CNV)  Olfaction  Sensory processing  Sensory processing measure (SPM)  Touch Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory processing atypicalities are frequent in Autism Spectrum Disorder (ASD) and neurodevelopmental disorders (NDD). Different domains of sensory processing appear to be differentially altered in these disorders. In this study, we explored the sensory profile of two clinical cohorts, in comparison with a sample of typically developing children. METHODS: Behavioral responses to sensory stimuli were assessed using the Sensory Processing Measure (parent-report questionnaire). We included 121 ASD children, 17 carriers of the 16p11.2 deletion (Del 16p11.2) and 45 typically developing (TD) children. All participants were aged between 2 and 12 years. Additional measures included the Tactile Defensiveness and Discrimination Test-Revised, Wechsler Intelligence Scales and Autism Diagnostic Observation Schedule (ADOS-2). Statistical analyses included MANCOVA and regression analyses. RESULTS: ASD children score significantly higher on all SPM subscales compared to TD. Del16p11.2 also scored higher than TD on all subscales except for tactile and olfactory/taste processing, in which they score similarly to TD. When assessing sensory modulation patterns (hyper-, hypo-responsiveness and seeking), ASD did not significantly differ from del16p11.2. Both groups had significantly higher scores across all patterns than the TD group. There was no significant association between the SPM Touch subscale and the TDDT-R. LIMITATIONS: Sensory processing was assessed using a parent-report questionnaire. Even though it captures observable behavior, a questionnaire does not assess sensory processing in all its complexity. The sample size of the genetic cohort and the small subset of ASD children with TDDT-R data render some of our results exploratory. Divergence between SPM Touch and TDDT-R raises important questions about the nature of the process that is assessed. CONCLUSIONS: Touch and olfaction/taste seem to be particularly affected in ASD children compared to del16p11.2. These results indicate that parent report measures can provide a useful perspective on behavioral expression. Sensory phenotyping, when combined with neurobiological and psychophysical methods, might have the potential to provide a better understanding of the sensory processing in ASD and in other NDD. En ligne : http://dx.doi.org/10.1186/s13229-020-00410-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Touch and olfaction/taste differentiate children carrying a 16p11.2 deletion from children with ASD [texte imprimé] / Joana Maria Almeida OSORIO, Auteur ; Borja RODRIGUEZ-HERREROS, Auteur ; David ROMASCANO, Auteur ; Vincent JUNOD, Auteur ; Aline HABEGGER, Auteur ; Aurélie PAIN, Auteur ; Sonia RICHETIN, Auteur ; Paola YU, Auteur ; Bertrand ISIDOR, Auteur ; Lionel VAN MALDERGEM, Auteur ; Linda PONS, Auteur ; Sabine MANIFICAT, Auteur ; Nadia CHABANE, Auteur ; Marine JEQUIER GYGAX, Auteur ; Anne Manuela MAILLARD, Auteur . - 8p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 8p. Mots-clés : 16p11.2 deletion  Autism spectrum disorder (ASD)  Children  Copy number variants (CNV)  Olfaction  Sensory processing  Sensory processing measure (SPM)  Touch Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory processing atypicalities are frequent in Autism Spectrum Disorder (ASD) and neurodevelopmental disorders (NDD). Different domains of sensory processing appear to be differentially altered in these disorders. In this study, we explored the sensory profile of two clinical cohorts, in comparison with a sample of typically developing children. METHODS: Behavioral responses to sensory stimuli were assessed using the Sensory Processing Measure (parent-report questionnaire). We included 121 ASD children, 17 carriers of the 16p11.2 deletion (Del 16p11.2) and 45 typically developing (TD) children. All participants were aged between 2 and 12 years. Additional measures included the Tactile Defensiveness and Discrimination Test-Revised, Wechsler Intelligence Scales and Autism Diagnostic Observation Schedule (ADOS-2). Statistical analyses included MANCOVA and regression analyses. RESULTS: ASD children score significantly higher on all SPM subscales compared to TD. Del16p11.2 also scored higher than TD on all subscales except for tactile and olfactory/taste processing, in which they score similarly to TD. When assessing sensory modulation patterns (hyper-, hypo-responsiveness and seeking), ASD did not significantly differ from del16p11.2. Both groups had significantly higher scores across all patterns than the TD group. There was no significant association between the SPM Touch subscale and the TDDT-R. LIMITATIONS: Sensory processing was assessed using a parent-report questionnaire. Even though it captures observable behavior, a questionnaire does not assess sensory processing in all its complexity. The sample size of the genetic cohort and the small subset of ASD children with TDDT-R data render some of our results exploratory. Divergence between SPM Touch and TDDT-R raises important questions about the nature of the process that is assessed. CONCLUSIONS: Touch and olfaction/taste seem to be particularly affected in ASD children compared to del16p11.2. These results indicate that parent report measures can provide a useful perspective on behavioral expression. Sensory phenotyping, when combined with neurobiological and psychophysical methods, might have the potential to provide a better understanding of the sensory processing in ASD and in other NDD. En ligne : http://dx.doi.org/10.1186/s13229-020-00410-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

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