Assessing the utility of electronic measures as a proxy for cognitive ability / Tess LEVY in Autism Research, 15-6 (June 2022)  

Public ISBD [article]  inAutism Research > 15-6 (June 2022) . - p.988-995 Titre : Assessing the utility of electronic measures as a proxy for cognitive ability Type de document : texte imprimé Auteurs : Tess LEVY, Auteur ; Bari BRITVAN, Auteur ; Hannah E. GROSMAN, Auteur ; Ivy GISERMAN-KISS, Auteur ; Kristin MEYERING, Auteur ; Jordana WEISSMAN, Auteur ; Danielle B. HALPERN, Auteur ; Jessica ZWEIFACH, Auteur ; M. Pilar TRELLES, Auteur ; Jennifer H. FOSS-FEIG, Auteur ; Alexander KOLEVZON, Auteur ; Stephan J. SANDERS, Auteur ; Elise B. ROBINSON, Auteur ; Joseph D. BUXBAUM, Auteur ; Somer L. BISHOP, Auteur ; Paige M. SIPER, Auteur Article en page(s) : p.988-995 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Large-scale genomic studies have identified over 100 genes associated with autism spectrum disorder (ASD); however, important phenotypic variables are captured inconsistently. In many cases, the resources required for comprehensive characterization hinder the feasibility of collecting critical information, such as intellectual ability. Thus, electronic collection of important phenotypes would greatly facilitate large-scale data collection efforts. This study assessed the utility of two electronic assessments as a proxy of cognitive ability relative to clinician-administered cognitive assessments. Ninety-two participants completed the study, including individuals with ASD (probands, n = 19), parents of probands (n = 46), and siblings without ASD (n = 27). Participants were administered the electronic-Peabody Picture Vocabulary Test, Fourth Edition (e-PPVT-4), an electronic visual reasoning (VR) test, and a clinician-administered Wechsler Abbreviated Scales of Intelligence, Second Edition (WASI-II). Probands also completed a full, in-person, cognitive assessment and Vineland Adaptive Behavior Scales, 2nd Edition. Correlations between scores on electronic and clinician-administered measures were examined. Classification accuracy of individual scores based on 95% confidence intervals and score range (below average, average, above average) were also assessed. Moderate to strong correlations were identified between both electronic measures and the clinician-administered WASI-II (? = 0.606 0.712). Mean difference between standard scores ranged from 10.7 to 14.8 for the cohort. Classification accuracy based on WASI-II 95% confidence interval was consistently low (27.5% 47.3%). Classification accuracy by score range (below average, average, above average) was variable, ranging from 33% to 86% for probands. All participants unable to complete the electronic assessments met DSM-5 criteria for intellectual disability. e-PPVT-4 and VR scores were strongly correlated with scores on the WASI-II full-scale IQ (? = 0.630, 0.712), indicating utility of these measures at the group level in large-scale genomic studies. However, the poor precision of measurement across both measures suggests that the e-PPVT-4 and VR are not useful alternatives to in-person testing for the purpose of clinical assessment of an individual's IQ score. Lay Summary Large-scale studies designed to identify genes associated with autism have been successful in identifying over 100 genes. However, important clinical information about participants with autism and their family members is often missed?including cognitive functioning. Cognitive testing requires in-person administration by a trained clinician and therefore can be burdensome and often reduces feasibility of diverse samples. Here, we assessed whether electronic assessments could take the place of in-person cognitive testing. We found that at the group level, for large-scale studies, electronic measures added valuable information; however, they were not accurate enough to be used on an individual level (i.e., to offer feedback about an individual's predicted IQ score). En ligne : https://doi.org/10.1002/aur.2704 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476 [article] Assessing the utility of electronic measures as a proxy for cognitive ability [texte imprimé] / Tess LEVY, Auteur ; Bari BRITVAN, Auteur ; Hannah E. GROSMAN, Auteur ; Ivy GISERMAN-KISS, Auteur ; Kristin MEYERING, Auteur ; Jordana WEISSMAN, Auteur ; Danielle B. HALPERN, Auteur ; Jessica ZWEIFACH, Auteur ; M. Pilar TRELLES, Auteur ; Jennifer H. FOSS-FEIG, Auteur ; Alexander KOLEVZON, Auteur ; Stephan J. SANDERS, Auteur ; Elise B. ROBINSON, Auteur ; Joseph D. BUXBAUM, Auteur ; Somer L. BISHOP, Auteur ; Paige M. SIPER, Auteur . - p.988-995. Langues : Anglais (eng) in Autism Research > 15-6 (June 2022) . - p.988-995 Index. décimale : PER Périodiques Résumé : Abstract Large-scale genomic studies have identified over 100 genes associated with autism spectrum disorder (ASD); however, important phenotypic variables are captured inconsistently. In many cases, the resources required for comprehensive characterization hinder the feasibility of collecting critical information, such as intellectual ability. Thus, electronic collection of important phenotypes would greatly facilitate large-scale data collection efforts. This study assessed the utility of two electronic assessments as a proxy of cognitive ability relative to clinician-administered cognitive assessments. Ninety-two participants completed the study, including individuals with ASD (probands, n = 19), parents of probands (n = 46), and siblings without ASD (n = 27). Participants were administered the electronic-Peabody Picture Vocabulary Test, Fourth Edition (e-PPVT-4), an electronic visual reasoning (VR) test, and a clinician-administered Wechsler Abbreviated Scales of Intelligence, Second Edition (WASI-II). Probands also completed a full, in-person, cognitive assessment and Vineland Adaptive Behavior Scales, 2nd Edition. Correlations between scores on electronic and clinician-administered measures were examined. Classification accuracy of individual scores based on 95% confidence intervals and score range (below average, average, above average) were also assessed. Moderate to strong correlations were identified between both electronic measures and the clinician-administered WASI-II (? = 0.606 0.712). Mean difference between standard scores ranged from 10.7 to 14.8 for the cohort. Classification accuracy based on WASI-II 95% confidence interval was consistently low (27.5% 47.3%). Classification accuracy by score range (below average, average, above average) was variable, ranging from 33% to 86% for probands. All participants unable to complete the electronic assessments met DSM-5 criteria for intellectual disability. e-PPVT-4 and VR scores were strongly correlated with scores on the WASI-II full-scale IQ (? = 0.630, 0.712), indicating utility of these measures at the group level in large-scale genomic studies. However, the poor precision of measurement across both measures suggests that the e-PPVT-4 and VR are not useful alternatives to in-person testing for the purpose of clinical assessment of an individual's IQ score. Lay Summary Large-scale studies designed to identify genes associated with autism have been successful in identifying over 100 genes. However, important clinical information about participants with autism and their family members is often missed?including cognitive functioning. Cognitive testing requires in-person administration by a trained clinician and therefore can be burdensome and often reduces feasibility of diverse samples. Here, we assessed whether electronic assessments could take the place of in-person cognitive testing. We found that at the group level, for large-scale studies, electronic measures added valuable information; however, they were not accurate enough to be used on an individual level (i.e., to offer feedback about an individual's predicted IQ score). En ligne : https://doi.org/10.1002/aur.2704 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476

Clinical, genetic, and cognitive correlates of seizure occurrences in Phelan-McDermid syndrome / Tess LEVY in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Clinical, genetic, and cognitive correlates of seizure occurrences in Phelan-McDermid syndrome Type de document : texte imprimé Auteurs : Tess LEVY, Auteur ; Jacob GLUCKMAN, Auteur ; Paige M. SIPER, Auteur ; Danielle HALPERN, Auteur ; Jessica ZWEIFACH, Auteur ; Rajna FILIP-DHIMA, Auteur ; J. Lloyd Jr HOLDER, Auteur ; M. Pilar TRELLES, Auteur ; Kristina JOHNSON, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Craig M. POWELL, Auteur ; Latha Valluripalli SOORYA, Auteur ; Audrey THURM, Auteur ; Joseph D. BUXBAUM, Auteur ; Mustafa SAHIN, Auteur ; Alexander KOLEVZON, Auteur ; Siddharth SRIVASTAVA, Auteur ; DEVELOPMENTAL SYNAPTOPATHIES CONSORTIUM, Auteur Langues : Anglais (eng) Mots-clés : Humans  Male  Female  Seizures/genetics  Chromosome Deletion  Chromosome Disorders/complications/genetics/physiopathology  Chromosomes, Human, Pair 22/genetics  Child  Child, Preschool  Adolescent  Longitudinal Studies  Young Adult  Adult  Prospective Studies  Infant  Nerve Tissue Proteins/genetics  22q13  Epilepsy  Phelan-McDermid syndrome  Shank3  Seizures Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by SHANK3 haploinsufficiency and is associated with an increased risk for seizures. Previous literature indicates that around one third of individuals with PMS also have epilepsy or seizures, with a wide range of types and ages of onset. Investigating the impact of seizures on intellectual and adaptive functioning for PMS is a primary concern for caregivers and is important to understanding the natural history of this syndrome. METHODS: We report on results from 98 individuals enrolled in a prospective, longitudinal study. We detailed seizure frequency, type, and age of onset, and we analyzed seizure occurrence with best estimate IQ, adaptive functioning, clinical features, and genotype. We conducted multiple linear regression analyses to assess the relationship between the presence of seizures and the Vineland Adaptive Behavior Scale, Second Edition (VABS-II) Adaptive Behavior Composite score and the best estimate full-scale IQ. We also performed Chi-square tests to explore associations between seizure prevalence and genetic groupings. Finally, we performed Chi-square tests and t-tests to explore the relationship between seizures and demographic features, features that manifest in infancy, and medical features. RESULTS: Seizures were present in 41% of the cohort, and age of onset was widely variable. The presence of seizures was associated with significantly lower adaptive and intellectual functioning. Genotype-phenotype analyses were discrepant, with no differences in seizure prevalence across genetic classes, but with more genes included in deletions of participants with 22q13 deletions and seizures compared to those with 22q13 deletions and no seizures. No clinical associations were found between the presence of seizures and sex, history of pre- or neonatal complications, early infancy, or medical features. In this cohort, generalized seizures were associated with developmental regression, which is a top concern for PMS caregivers. CONCLUSIONS: These results begin to eludicate correlates of seizures in individuals with PMS and highlight the importance of early seizure management. Importantly, presence of seizures was associated with adaptive and cognitive functioning. A larger cohort might be able to identify additional associations with medical features. Genetic findings suggest an increased capability to realize genotype-phenotype relationships when deletion size is taken into account. En ligne : https://dx.doi.org/10.1186/s11689-024-09541-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Clinical, genetic, and cognitive correlates of seizure occurrences in Phelan-McDermid syndrome [texte imprimé] / Tess LEVY, Auteur ; Jacob GLUCKMAN, Auteur ; Paige M. SIPER, Auteur ; Danielle HALPERN, Auteur ; Jessica ZWEIFACH, Auteur ; Rajna FILIP-DHIMA, Auteur ; J. Lloyd Jr HOLDER, Auteur ; M. Pilar TRELLES, Auteur ; Kristina JOHNSON, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Craig M. POWELL, Auteur ; Latha Valluripalli SOORYA, Auteur ; Audrey THURM, Auteur ; Joseph D. BUXBAUM, Auteur ; Mustafa SAHIN, Auteur ; Alexander KOLEVZON, Auteur ; Siddharth SRIVASTAVA, Auteur ; DEVELOPMENTAL SYNAPTOPATHIES CONSORTIUM, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Male  Female  Seizures/genetics  Chromosome Deletion  Chromosome Disorders/complications/genetics/physiopathology  Chromosomes, Human, Pair 22/genetics  Child  Child, Preschool  Adolescent  Longitudinal Studies  Young Adult  Adult  Prospective Studies  Infant  Nerve Tissue Proteins/genetics  22q13  Epilepsy  Phelan-McDermid syndrome  Shank3  Seizures Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by SHANK3 haploinsufficiency and is associated with an increased risk for seizures. Previous literature indicates that around one third of individuals with PMS also have epilepsy or seizures, with a wide range of types and ages of onset. Investigating the impact of seizures on intellectual and adaptive functioning for PMS is a primary concern for caregivers and is important to understanding the natural history of this syndrome. METHODS: We report on results from 98 individuals enrolled in a prospective, longitudinal study. We detailed seizure frequency, type, and age of onset, and we analyzed seizure occurrence with best estimate IQ, adaptive functioning, clinical features, and genotype. We conducted multiple linear regression analyses to assess the relationship between the presence of seizures and the Vineland Adaptive Behavior Scale, Second Edition (VABS-II) Adaptive Behavior Composite score and the best estimate full-scale IQ. We also performed Chi-square tests to explore associations between seizure prevalence and genetic groupings. Finally, we performed Chi-square tests and t-tests to explore the relationship between seizures and demographic features, features that manifest in infancy, and medical features. RESULTS: Seizures were present in 41% of the cohort, and age of onset was widely variable. The presence of seizures was associated with significantly lower adaptive and intellectual functioning. Genotype-phenotype analyses were discrepant, with no differences in seizure prevalence across genetic classes, but with more genes included in deletions of participants with 22q13 deletions and seizures compared to those with 22q13 deletions and no seizures. No clinical associations were found between the presence of seizures and sex, history of pre- or neonatal complications, early infancy, or medical features. In this cohort, generalized seizures were associated with developmental regression, which is a top concern for PMS caregivers. CONCLUSIONS: These results begin to eludicate correlates of seizures in individuals with PMS and highlight the importance of early seizure management. Importantly, presence of seizures was associated with adaptive and cognitive functioning. A larger cohort might be able to identify additional associations with medical features. Genetic findings suggest an increased capability to realize genotype-phenotype relationships when deletion size is taken into account. En ligne : https://dx.doi.org/10.1186/s11689-024-09541-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome / Alexander KOLEVZON in Molecular Autism, 13 (2022)  

Public ISBD [article]  inMolecular Autism > 13 (2022) . - 17 p. Titre : Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome Type de document : texte imprimé Auteurs : Alexander KOLEVZON, Auteur ; Michael S. BREEN, Auteur ; Paige M. SIPER, Auteur ; Danielle B. HALPERN, Auteur ; Yitzchak FRANK, Auteur ; H. RIEGER, Auteur ; J. WEISMANN, Auteur ; Maria Del Pilar TRELLES, Auteur ; Bonnie LERMAN, Auteur ; Robert RAPAPORT, Auteur ; Joseph D. BUXBAUM, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Mots-clés : Child  Chromosome Deletion  Chromosome Disorders/drug therapy/genetics  Chromosomes, Human, Pair 22  Humans  Insulin-Like Growth Factor I/therapeutic use  Pilot Projects  Asd  Autism spectrum disorder  Igf-1  Insulin-like growth factor-1  Pms  Phelan-McDermid syndrome  shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. METHODS: Ten children aged 5-9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N=19). RESULTS: Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. LIMITATIONS: The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. CONCLUSION: IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity in children with PMS. Trial registration NCT01525901. En ligne : http://dx.doi.org/10.1186/s13229-022-00493-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 [article] Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome [texte imprimé] / Alexander KOLEVZON, Auteur ; Michael S. BREEN, Auteur ; Paige M. SIPER, Auteur ; Danielle B. HALPERN, Auteur ; Yitzchak FRANK, Auteur ; H. RIEGER, Auteur ; J. WEISMANN, Auteur ; Maria Del Pilar TRELLES, Auteur ; Bonnie LERMAN, Auteur ; Robert RAPAPORT, Auteur ; Joseph D. BUXBAUM, Auteur . - 17 p. Langues : Anglais (eng) in Molecular Autism > 13 (2022) . - 17 p. Mots-clés : Child  Chromosome Deletion  Chromosome Disorders/drug therapy/genetics  Chromosomes, Human, Pair 22  Humans  Insulin-Like Growth Factor I/therapeutic use  Pilot Projects  Asd  Autism spectrum disorder  Igf-1  Insulin-like growth factor-1  Pms  Phelan-McDermid syndrome  shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. METHODS: Ten children aged 5-9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N=19). RESULTS: Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. LIMITATIONS: The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. CONCLUSION: IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity in children with PMS. Trial registration NCT01525901. En ligne : http://dx.doi.org/10.1186/s13229-022-00493-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477

Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations / Silvia DE RUBEIS in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 31p. Titre : Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations Type de document : texte imprimé Auteurs : Silvia DE RUBEIS, Auteur ; Paige M. SIPER, Auteur ; Allison DURKIN, Auteur ; Jordana WEISSMAN, Auteur ; François MURATET, Auteur ; Danielle B. HALPERN, Auteur ; Maria Del Pilar TRELLES, Auteur ; Yitzchak FRANK, Auteur ; Reymundo LOZANO, Auteur ; A. Ting WANG, Auteur ; J. Lloyd HOLDER, Auteur ; Catalina BETANCUR, Auteur ; Joseph D. BUXBAUM, Auteur ; Alexander KOLEVZON, Auteur Article en page(s) : 31p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Child  Child, Preschool  Chromosome Deletion  Chromosome Disorders/genetics/pathology  Chromosomes, Human, Pair 22/genetics  Female  Haploinsufficiency  Humans  Male  Nerve Tissue Proteins/genetics  Phenotype  Point Mutation  22q13 deletion syndrome  Autism spectrum disorder  Intellectual disability  Phelan-McDermid syndrome  shank3  Sequence variants Index. décimale : PER Périodiques Résumé : Background: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by psychiatric and neurological features. Most reported cases are caused by 22q13.3 deletions, leading to SHANK3 haploinsufficiency, but also usually encompassing many other genes. While the number of point mutations identified in SHANK3 has increased in recent years due to large-scale sequencing studies, systematic studies describing the phenotype of individuals harboring such mutations are lacking. Methods: We provide detailed clinical and genetic data on 17 individuals carrying mutations in SHANK3. We also review 60 previously reported patients with pathogenic or likely pathogenic SHANK3 variants, often lacking detailed phenotypic information. Results: SHANK3 mutations in our cohort and in previously reported cases were distributed throughout the protein; the majority were truncating and all were compatible with de novo inheritance. Despite substantial allelic heterogeneity, four variants were recurrent (p.Leu1142Valfs*153, p.Ala1227Glyfs*69, p.Arg1255Leufs*25, and c.2265+1G>A), suggesting that these are hotspots for de novo mutations. All individuals studied had intellectual disability, and autism spectrum disorder was prevalent (73%). Severe speech deficits were common, but in contrast to individuals with 22q13.3 deletions, the majority developed single words, including 41% with at least phrase speech. Other common findings were consistent with reports among individuals with 22q13.3 deletions, including hypotonia, motor skill deficits, regression, seizures, brain abnormalities, mild dysmorphic features, and feeding and gastrointestinal problems. Conclusions: Haploinsufficiency of SHANK3 resulting from point mutations is sufficient to cause a broad range of features associated with PMS. Our findings expand the molecular and phenotypic spectrum of PMS caused by SHANK3 point mutations and suggest that, in general, speech impairment and motor deficits are more severe in the case of deletions. In contrast, renal abnormalities associated with 22q13.3 deletions do not appear to be related to the loss of SHANK3. En ligne : https://dx.doi.org/10.1186/s13229-018-0205-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations [texte imprimé] / Silvia DE RUBEIS, Auteur ; Paige M. SIPER, Auteur ; Allison DURKIN, Auteur ; Jordana WEISSMAN, Auteur ; François MURATET, Auteur ; Danielle B. HALPERN, Auteur ; Maria Del Pilar TRELLES, Auteur ; Yitzchak FRANK, Auteur ; Reymundo LOZANO, Auteur ; A. Ting WANG, Auteur ; J. Lloyd HOLDER, Auteur ; Catalina BETANCUR, Auteur ; Joseph D. BUXBAUM, Auteur ; Alexander KOLEVZON, Auteur . - 31p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 31p. Mots-clés : Adolescent  Adult  Child  Child, Preschool  Chromosome Deletion  Chromosome Disorders/genetics/pathology  Chromosomes, Human, Pair 22/genetics  Female  Haploinsufficiency  Humans  Male  Nerve Tissue Proteins/genetics  Phenotype  Point Mutation  22q13 deletion syndrome  Autism spectrum disorder  Intellectual disability  Phelan-McDermid syndrome  shank3  Sequence variants Index. décimale : PER Périodiques Résumé : Background: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by psychiatric and neurological features. Most reported cases are caused by 22q13.3 deletions, leading to SHANK3 haploinsufficiency, but also usually encompassing many other genes. While the number of point mutations identified in SHANK3 has increased in recent years due to large-scale sequencing studies, systematic studies describing the phenotype of individuals harboring such mutations are lacking. Methods: We provide detailed clinical and genetic data on 17 individuals carrying mutations in SHANK3. We also review 60 previously reported patients with pathogenic or likely pathogenic SHANK3 variants, often lacking detailed phenotypic information. Results: SHANK3 mutations in our cohort and in previously reported cases were distributed throughout the protein; the majority were truncating and all were compatible with de novo inheritance. Despite substantial allelic heterogeneity, four variants were recurrent (p.Leu1142Valfs*153, p.Ala1227Glyfs*69, p.Arg1255Leufs*25, and c.2265+1G>A), suggesting that these are hotspots for de novo mutations. All individuals studied had intellectual disability, and autism spectrum disorder was prevalent (73%). Severe speech deficits were common, but in contrast to individuals with 22q13.3 deletions, the majority developed single words, including 41% with at least phrase speech. Other common findings were consistent with reports among individuals with 22q13.3 deletions, including hypotonia, motor skill deficits, regression, seizures, brain abnormalities, mild dysmorphic features, and feeding and gastrointestinal problems. Conclusions: Haploinsufficiency of SHANK3 resulting from point mutations is sufficient to cause a broad range of features associated with PMS. Our findings expand the molecular and phenotypic spectrum of PMS caused by SHANK3 point mutations and suggest that, in general, speech impairment and motor deficits are more severe in the case of deletions. In contrast, renal abnormalities associated with 22q13.3 deletions do not appear to be related to the loss of SHANK3. En ligne : https://dx.doi.org/10.1186/s13229-018-0205-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

Examining the Efficacy of a Family Peer Advocate Model for Black and Hispanic Caregivers of Children with Autism Spectrum Disorder / J.M. JAMISON in Journal of Autism and Developmental Disorders, 47-5 (May 2017)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 47-5 (May 2017) . - p.1314-1322 Titre : Examining the Efficacy of a Family Peer Advocate Model for Black and Hispanic Caregivers of Children with Autism Spectrum Disorder Type de document : texte imprimé Auteurs : J.M. JAMISON, Auteur ; Emily FOURIE, Auteur ; Paige M. SIPER, Auteur ; Maria Del Pilar TRELLES, Auteur ; Julia GEORGE-JONES, Auteur ; A. BUXBAUM GRICE, Auteur ; J. KRATA, Auteur ; E. HOLL, Auteur ; J. SHAOUL, Auteur ; B. HERNANDEZ, Auteur ; L. MITCHELL, Auteur ; Renée M. MCKAY, Auteur ; Joseph D. BUXBAUM, Auteur ; Alexander KOLEVZON, Auteur Article en page(s) : p.1314-1322 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Family peer advocate  Minority  Caregiver stress Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) affects individuals across all racial and ethnic groups, yet rates of diagnosis are disproportionately higher for Black and Hispanic children. Caregivers of children with ASD experience significant stressors, which have been associated with parental strain, inadequate utilization of mental health services and lower quality of life. The family peer advocate (FPA) model has been utilized across service delivery systems to provide family-to-family support, facilitate engagement, and increase access to care. This study used a randomized controlled design to examine the efficacy of FPAs in a racially and ethnically diverse sample. Results demonstrate significantly increased knowledge of ASD and reduced levels of stress for caregivers who received the FPA intervention as compared to treatment as usual. En ligne : http://dx.doi.org/10.1007/s10803-017-3045-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=305 [article] Examining the Efficacy of a Family Peer Advocate Model for Black and Hispanic Caregivers of Children with Autism Spectrum Disorder [texte imprimé] / J.M. JAMISON, Auteur ; Emily FOURIE, Auteur ; Paige M. SIPER, Auteur ; Maria Del Pilar TRELLES, Auteur ; Julia GEORGE-JONES, Auteur ; A. BUXBAUM GRICE, Auteur ; J. KRATA, Auteur ; E. HOLL, Auteur ; J. SHAOUL, Auteur ; B. HERNANDEZ, Auteur ; L. MITCHELL, Auteur ; Renée M. MCKAY, Auteur ; Joseph D. BUXBAUM, Auteur ; Alexander KOLEVZON, Auteur . - p.1314-1322. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 47-5 (May 2017) . - p.1314-1322 Mots-clés : Autism spectrum disorder  Family peer advocate  Minority  Caregiver stress Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) affects individuals across all racial and ethnic groups, yet rates of diagnosis are disproportionately higher for Black and Hispanic children. Caregivers of children with ASD experience significant stressors, which have been associated with parental strain, inadequate utilization of mental health services and lower quality of life. The family peer advocate (FPA) model has been utilized across service delivery systems to provide family-to-family support, facilitate engagement, and increase access to care. This study used a randomized controlled design to examine the efficacy of FPAs in a racially and ethnically diverse sample. Results demonstrate significantly increased knowledge of ASD and reduced levels of stress for caregivers who received the FPA intervention as compared to treatment as usual. En ligne : http://dx.doi.org/10.1007/s10803-017-3045-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=305

Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder / Stephen K. SIECINSKI in Autism Research, 16-3 (March 2023)  

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Individuals with FOXP1 syndrome present with a complex neurobehavioral profile with high rates of ADHD, anxiety, repetitive behaviors, and sensory symptoms / Maria Del Pilar TRELLES in Molecular Autism, 12 (2021)  

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Prospective investigation of FOXP1 syndrome / Paige M. SIPER in Molecular Autism, 8 (2017)  

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Psychiatric illness and regression in individuals with Phelan-McDermid syndrome / Teresa M. KOHLENBERG in Journal of Neurodevelopmental Disorders, 12 (2020)  

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Psychometric Study of the Social Responsiveness Scale in Phelan-McDermid Syndrome / Kellie GERGOUDIS in Autism Research, 13-8 (August 2020)  

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Reduced engagement of visual attention in children with autism spectrum disorder / Christopher S. MCLAUGHLIN in Autism, 25-7 (October 2021)  

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Reduced engagement of visual attention in children with autism spectrum disorder / Christopher S. MCLAUGHLIN in Autism, 26-7 (October 2022)  

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Social visual attentional engagement and memory in Phelan-McDermid syndrome and autism spectrum disorder: a pilot eye tracking study / Sylvia B. GUILLORY in Journal of Neurodevelopmental Disorders, 13 (2021)  

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