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 et/ou numérique Auteurs : Tess LEVY, Auteur ; Bari BRITVAN, Auteur ; Hannah 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 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 et/ou numérique] / Tess LEVY, Auteur ; Bari BRITVAN, Auteur ; Hannah 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 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

Children with autism spectrum disorder who improve with fever: Insights from the Simons Simplex Collection / Rebecca GRZADZINSKI in Autism Research, 11-1 (January 2018)  

Public ISBD [article]  inAutism Research > 11-1 (January 2018) . - p.175-184 Titre : Children with autism spectrum disorder who improve with fever: Insights from the Simons Simplex Collection Type de document : Texte imprimé et/ou numérique Auteurs : Rebecca GRZADZINSKI, Auteur ; Catherine LORD, Auteur ; Stephan J. SANDERS, Auteur ; Donna WERLING, Auteur ; Vanessa H. BAL, Auteur Article en page(s) : p.175-184 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Literature indicates that some children with ASD may show behavioral improvements during fever; however, little is known about the behavioral profiles of these children. This study aims to (a) investigate the subset of children who show parent?reported behavioral improvements associated with fever and (b) compare the demographic, behavioral, and genetic characteristics of this subset of children to children whose parents report no change during fever. Parents of 2,152 children from the Simons Simplex Collection provided information about whether and in which areas their child improved during fever. Children were randomly assigned into discovery or replication samples. In discovery analyses, children who reportedly improved with fever (Improve Group) were compared to those who reportedly did not improve (No Improve Group) on demographics, medical history, ASD symptoms, adaptive skills, and presence of de novo ASD?associated mutations. Significant and marginal results from discovery analyses were tested in the replication sample. Parent reports of 17% of children indicated improvements during fever across a range of domains. Discovery and replication analyses revealed that the Improve Group had significantly lower non?verbal cognitive skills (NVIQ) and language levels and more repetitive behaviors. Groups did not differ on demographic variables, parent?report of current ASD symptoms or the presence of de novo mutations. Understanding the profiles of children who improve during episodes of fever may provide insights into innovative treatments for ASD. Autism Res 2018, 11: 175–184. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary This study explored characteristics of children with ASD who are reported to improve during fever. Parents of 17% of children with ASD report improvements across a range of domains during fever including cognition, communication, repetitive behaviors, social interaction, and behavior. Children who are reported to improve during fever have significantly lower non?verbal cognitive skills and language levels and more repetitive behaviors. Understanding the profiles of children who improve during episodes of fever may provide insights into new treatments for ASD. En ligne : https://doi.org/10.1002/aur.1856 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=334 [article] Children with autism spectrum disorder who improve with fever: Insights from the Simons Simplex Collection [Texte imprimé et/ou numérique] / Rebecca GRZADZINSKI, Auteur ; Catherine LORD, Auteur ; Stephan J. SANDERS, Auteur ; Donna WERLING, Auteur ; Vanessa H. BAL, Auteur . - p.175-184. Langues : Anglais (eng) in Autism Research > 11-1 (January 2018) . - p.175-184 Index. décimale : PER Périodiques Résumé : Literature indicates that some children with ASD may show behavioral improvements during fever; however, little is known about the behavioral profiles of these children. This study aims to (a) investigate the subset of children who show parent?reported behavioral improvements associated with fever and (b) compare the demographic, behavioral, and genetic characteristics of this subset of children to children whose parents report no change during fever. Parents of 2,152 children from the Simons Simplex Collection provided information about whether and in which areas their child improved during fever. Children were randomly assigned into discovery or replication samples. In discovery analyses, children who reportedly improved with fever (Improve Group) were compared to those who reportedly did not improve (No Improve Group) on demographics, medical history, ASD symptoms, adaptive skills, and presence of de novo ASD?associated mutations. Significant and marginal results from discovery analyses were tested in the replication sample. Parent reports of 17% of children indicated improvements during fever across a range of domains. Discovery and replication analyses revealed that the Improve Group had significantly lower non?verbal cognitive skills (NVIQ) and language levels and more repetitive behaviors. Groups did not differ on demographic variables, parent?report of current ASD symptoms or the presence of de novo mutations. Understanding the profiles of children who improve during episodes of fever may provide insights into innovative treatments for ASD. Autism Res 2018, 11: 175–184. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary This study explored characteristics of children with ASD who are reported to improve during fever. Parents of 17% of children with ASD report improvements across a range of domains during fever including cognition, communication, repetitive behaviors, social interaction, and behavior. Children who are reported to improve during fever have significantly lower non?verbal cognitive skills and language levels and more repetitive behaviors. Understanding the profiles of children who improve during episodes of fever may provide insights into new treatments for ASD. En ligne : https://doi.org/10.1002/aur.1856 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=334

Common genetic variants, acting additively, are a major source of risk for autism / Lambertus KLEI in Molecular Autism, (October 2012)  

Public ISBD [article]  inMolecular Autism > (October 2012) . - 13 p. Titre : Common genetic variants, acting additively, are a major source of risk for autism Type de document : Texte imprimé et/ou numérique Auteurs : Lambertus KLEI, Auteur ; Stephan J. SANDERS, Auteur ; Michael T. MURTHA, Auteur ; Vanessa HUS, Auteur ; Jennifer K. LOWE, Auteur ; A. J. WILLSEY, Auteur ; Daniel MORENO DE LUCA, Auteur ; Timothy W. YU, Auteur ; Eric FOMBONNE, Auteur ; Daniel H. GESCHWIND, Auteur ; Dorothy E. GRICE, Auteur ; David H. LEDBETTER, Auteur ; Catherine LORD, Auteur ; Shrikant M. MANE, Auteur ; Christa L. MARTIN, Auteur ; Donna M. MARTIN, Auteur ; Eric M. MORROW, Auteur ; Christopher A. WALSH, Auteur ; Nadine M. MELHEM, Auteur ; Pauline CHASTE, Auteur ; James S. SUTCLIFFE, Auteur ; Matthew W. STATE, Auteur ; Edwin H. Jr COOK, Auteur ; Kathryn ROEDER, Auteur ; Bernie DEVLIN, Auteur Année de publication : 2012 Article en page(s) : 13 p. Langues : Anglais (eng) Mots-clés : Narrow-sense heritability  Multiplex  Simplex  Quantitative genetics Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. Methods By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. Results By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Conclusions Our results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability. En ligne : http://dx.doi.org/10.1186/2040-2392-3-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Common genetic variants, acting additively, are a major source of risk for autism [Texte imprimé et/ou numérique] / Lambertus KLEI, Auteur ; Stephan J. SANDERS, Auteur ; Michael T. MURTHA, Auteur ; Vanessa HUS, Auteur ; Jennifer K. LOWE, Auteur ; A. J. WILLSEY, Auteur ; Daniel MORENO DE LUCA, Auteur ; Timothy W. YU, Auteur ; Eric FOMBONNE, Auteur ; Daniel H. GESCHWIND, Auteur ; Dorothy E. GRICE, Auteur ; David H. LEDBETTER, Auteur ; Catherine LORD, Auteur ; Shrikant M. MANE, Auteur ; Christa L. MARTIN, Auteur ; Donna M. MARTIN, Auteur ; Eric M. MORROW, Auteur ; Christopher A. WALSH, Auteur ; Nadine M. MELHEM, Auteur ; Pauline CHASTE, Auteur ; James S. SUTCLIFFE, Auteur ; Matthew W. STATE, Auteur ; Edwin H. Jr COOK, Auteur ; Kathryn ROEDER, Auteur ; Bernie DEVLIN, Auteur . - 2012 . - 13 p. Langues : Anglais (eng) in Molecular Autism > (October 2012) . - 13 p. Mots-clés : Narrow-sense heritability  Multiplex  Simplex  Quantitative genetics Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. Methods By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. Results By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Conclusions Our results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability. En ligne : http://dx.doi.org/10.1186/2040-2392-3-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

DAWN: a framework to identify autism genes and subnetworks using gene expression and genetics / Li LIU in Molecular Autism, (March 2014)  

Public ISBD [article]  inMolecular Autism > (March 2014) . - p.1-18 Titre : DAWN: a framework to identify autism genes and subnetworks using gene expression and genetics Type de document : Texte imprimé et/ou numérique Auteurs : Li LIU, Auteur ; Jing LEI, Auteur ; Stephan J. SANDERS, Auteur ; Arthur Jeremy WILLSEY, Auteur ; Yan KOU, Auteur ; Abdullah Ercument CICEK, Auteur ; Lambertus KLEI, Auteur ; Cong LU, Auteur ; Xin HE, Auteur ; Mingfeng LI, Auteur ; Rebecca A. MUHLE, Auteur ; Avi MA’AYAN, Auteur ; James P. NOONAN, Auteur ; Nenad ŠESTAN, Auteur ; Kathryn A. MCFADDEN, Auteur ; Matthew W. STATE, Auteur ; Joseph D. BUXBAUM, Auteur ; Bernie DEVLIN, Auteur ; Kathryn ROEDER, Auteur Article en page(s) : p.1-18 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : De novo loss-of-function (dnLoF) mutations are found twofold more often in autism spectrum disorder (ASD) probands than their unaffected siblings. Multiple independent dnLoF mutations in the same gene implicate the gene in risk and hence provide a systematic, albeit arduous, path forward for ASD genetics. It is likely that using additional non-genetic data will enhance the ability to identify ASD genes. En ligne : http://dx.doi.org/10.1186/2040-2392-5-22 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276 [article] DAWN: a framework to identify autism genes and subnetworks using gene expression and genetics [Texte imprimé et/ou numérique] / Li LIU, Auteur ; Jing LEI, Auteur ; Stephan J. SANDERS, Auteur ; Arthur Jeremy WILLSEY, Auteur ; Yan KOU, Auteur ; Abdullah Ercument CICEK, Auteur ; Lambertus KLEI, Auteur ; Cong LU, Auteur ; Xin HE, Auteur ; Mingfeng LI, Auteur ; Rebecca A. MUHLE, Auteur ; Avi MA’AYAN, Auteur ; James P. NOONAN, Auteur ; Nenad ŠESTAN, Auteur ; Kathryn A. MCFADDEN, Auteur ; Matthew W. STATE, Auteur ; Joseph D. BUXBAUM, Auteur ; Bernie DEVLIN, Auteur ; Kathryn ROEDER, Auteur . - p.1-18. Langues : Anglais (eng) in Molecular Autism > (March 2014) . - p.1-18 Index. décimale : PER Périodiques Résumé : De novo loss-of-function (dnLoF) mutations are found twofold more often in autism spectrum disorder (ASD) probands than their unaffected siblings. Multiple independent dnLoF mutations in the same gene implicate the gene in risk and hence provide a systematic, albeit arduous, path forward for ASD genetics. It is likely that using additional non-genetic data will enhance the ability to identify ASD genes. En ligne : http://dx.doi.org/10.1186/2040-2392-5-22 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276

Modest Impact on Risk for Autism Spectrum Disorder of Rare Copy Number Variants at 15q11.2, Specifically Breakpoints 1 to 2 / Pauline CHASTE in Autism Research, 7-3 (June 2014)  

Public ISBD [article]  inAutism Research > 7-3 (June 2014) . - p.355-362 Titre : Modest Impact on Risk for Autism Spectrum Disorder of Rare Copy Number Variants at 15q11.2, Specifically Breakpoints 1 to 2 Type de document : Texte imprimé et/ou numérique Auteurs : Pauline CHASTE, Auteur ; Stephan J. SANDERS, Auteur ; Kommu N. MOHAN, Auteur ; Lambertus KLEI, Auteur ; Youeun SONG, Auteur ; Michael T. MURTHA, Auteur ; Vanessa HUS, Auteur ; Jennifer K. LOWE, Auteur ; A. Jeremy WILLSEY, Auteur ; Daniel MORENO-DE-LUCA, Auteur ; Timothy W. YU, Auteur ; Eric FOMBONNE, Auteur ; Daniel H. GESCHWIND, Auteur ; Dorothy E. GRICE, Auteur ; David H. LEDBETTER, Auteur ; Catherine LORD, Auteur ; Shrikant M. MANE, Auteur ; Donna M. MARTIN, Auteur ; Eric M. MORROW, Auteur ; Christopher A. WALSH, Auteur ; James S. SUTCLIFFE, Auteur ; Matthew W. STATE, Auteur ; Christa Lese MARTIN, Auteur ; Bernie DEVLIN, Auteur ; Arthur L. BEAUDET, Auteur ; Edwin H. Jr COOK, Auteur ; Soo-Jeong KIM, Auteur Article en page(s) : p.355-362 Langues : Anglais (eng) Mots-clés : 15q11.2  deletion  duplication  penetrance  autism Index. décimale : PER Périodiques Résumé : The proximal region of chromosome 15 is one of the genomic hotspots for copy number variants (CNVs). Among the rearrangements observed in this region, CNVs from the interval between the common breakpoints 1 and 2 (BP1 and BP2) have been reported cosegregating with autism spectrum disorder (ASD). Although evidence supporting an association between BP1-BP2 CNVs and autism accumulates, the magnitude of the effect of BP1-BP2 CNVs remains elusive, posing a great challenge to recurrence-risk counseling. To gain further insight into their pathogenicity for ASD, we estimated the penetrance of the BP1-BP2 CNVs for ASD as well as their effects on ASD-related phenotypes in a well-characterized ASD sample (n?=?2525 families). Transmission disequilibrium test revealed significant preferential transmission only for the duplicated chromosome in probands (20T:9NT). The penetrance of the BP1-BP2 CNVs for ASD was low, conferring additional risks of 0.3% (deletion) and 0.8% (duplication). Stepwise regression analyses suggest a greater effect of the CNVs on ASD-related phenotype in males and when maternally inherited. Taken together, the results are consistent with BP1-BP2 CNVs as risk factors for autism. However, their effect is modest, more akin to that seen for common variants. To be consistent with the current American College of Medical Genetics guidelines for interpretation of postnatal CNV, the BP1-BP2 deletion and duplication CNVs would probably best be classified as variants of uncertain significance (VOUS): they appear to have an impact on risk, but one so modest that these CNVs do not merit pathogenic status. Autism Res 2014, 7: 355–362. © 2014 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1378 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=235 [article] Modest Impact on Risk for Autism Spectrum Disorder of Rare Copy Number Variants at 15q11.2, Specifically Breakpoints 1 to 2 [Texte imprimé et/ou numérique] / Pauline CHASTE, Auteur ; Stephan J. SANDERS, Auteur ; Kommu N. MOHAN, Auteur ; Lambertus KLEI, Auteur ; Youeun SONG, Auteur ; Michael T. MURTHA, Auteur ; Vanessa HUS, Auteur ; Jennifer K. LOWE, Auteur ; A. Jeremy WILLSEY, Auteur ; Daniel MORENO-DE-LUCA, Auteur ; Timothy W. YU, Auteur ; Eric FOMBONNE, Auteur ; Daniel H. GESCHWIND, Auteur ; Dorothy E. GRICE, Auteur ; David H. LEDBETTER, Auteur ; Catherine LORD, Auteur ; Shrikant M. MANE, Auteur ; Donna M. MARTIN, Auteur ; Eric M. MORROW, Auteur ; Christopher A. WALSH, Auteur ; James S. SUTCLIFFE, Auteur ; Matthew W. STATE, Auteur ; Christa Lese MARTIN, Auteur ; Bernie DEVLIN, Auteur ; Arthur L. BEAUDET, Auteur ; Edwin H. Jr COOK, Auteur ; Soo-Jeong KIM, Auteur . - p.355-362. Langues : Anglais (eng) in Autism Research > 7-3 (June 2014) . - p.355-362 Mots-clés : 15q11.2  deletion  duplication  penetrance  autism Index. décimale : PER Périodiques Résumé : The proximal region of chromosome 15 is one of the genomic hotspots for copy number variants (CNVs). Among the rearrangements observed in this region, CNVs from the interval between the common breakpoints 1 and 2 (BP1 and BP2) have been reported cosegregating with autism spectrum disorder (ASD). Although evidence supporting an association between BP1-BP2 CNVs and autism accumulates, the magnitude of the effect of BP1-BP2 CNVs remains elusive, posing a great challenge to recurrence-risk counseling. To gain further insight into their pathogenicity for ASD, we estimated the penetrance of the BP1-BP2 CNVs for ASD as well as their effects on ASD-related phenotypes in a well-characterized ASD sample (n?=?2525 families). Transmission disequilibrium test revealed significant preferential transmission only for the duplicated chromosome in probands (20T:9NT). The penetrance of the BP1-BP2 CNVs for ASD was low, conferring additional risks of 0.3% (deletion) and 0.8% (duplication). Stepwise regression analyses suggest a greater effect of the CNVs on ASD-related phenotype in males and when maternally inherited. Taken together, the results are consistent with BP1-BP2 CNVs as risk factors for autism. However, their effect is modest, more akin to that seen for common variants. To be consistent with the current American College of Medical Genetics guidelines for interpretation of postnatal CNV, the BP1-BP2 deletion and duplication CNVs would probably best be classified as variants of uncertain significance (VOUS): they appear to have an impact on risk, but one so modest that these CNVs do not merit pathogenic status. Autism Res 2014, 7: 355–362. © 2014 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1378 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=235

Peabody Picture Vocabulary Test: Proxy for Verbal IQ in Genetic Studies of Autism Spectrum Disorder / Kate E. KRASILEVA in Journal of Autism and Developmental Disorders, 47-4 (April 2017)  

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Prenatal exposure to paternal smoking and likelihood for autism spectrum disorder / Bora KIM in Autism, 26-7 (October 2022)  

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Sex and gender differences in autism spectrum disorder: summarizing evidence gaps and identifying emerging areas of priority / Alycia K. HALLADAY in Molecular Autism, (June 2015)  

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The female protective effect in autism spectrum disorder is not mediated by a single genetic locus / Jake GOCKLEY in Molecular Autism, (May 2015)  

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