Autism and the broad autism phenotype: familial patterns and intergenerational transmission / Noah J. SASSON in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.11 Titre : Autism and the broad autism phenotype: familial patterns and intergenerational transmission Type de document : Texte imprimé et/ou numérique Auteurs : Noah J. SASSON, Auteur ; K. S. LAM, Auteur ; M. PARLIER, Auteur ; Julie L. DANIELS, Auteur ; J. PIVEN, Auteur Article en page(s) : p.11 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Features of the Broad Autism Phenotype (BAP) are disproportionately prevalent in parents of a child with autism, highlighting familial patterns indicative of heritability. It is unclear, however, whether the presence of BAP features in both parents confers an increased liability for autism. The current study explores whether the presence of BAP features in two biological parents occurs more frequently in parents of a child with autism relative to comparison parents, whether parental pairs of a child with autism more commonly consist of one or two parents with BAP features, and whether these features are associated with severity of autism behaviors in probands. METHOD: Seven hundred eleven parents of a child with an autism spectrum disorder and 981 comparison parents completed the Broad Autism Phenotype Questionnaire. Parents of a child with autism also completed the Social Communication Questionnaire. RESULTS: Although parental pairs of a child with autism were more likely than comparison parental pairs to have both parents characterized by the presence of the BAP, they more commonly consisted of a single parent with BAP features. The presence of the BAP in parents was associated with the severity of autism behaviors in probands, with the lowest severity occurring for children of parental pairs in which neither parent exhibited a BAP feature. Severity did not differ between children of two affected parents and those of just one. CONCLUSIONS: Collectively, these findings indicate that parental pairs of children with autism frequently consist of a single parent with BAP characteristics and suggest that future studies searching for implicated genes may benefit from a more narrow focus that identifies the transmitting parent. The evidence of intergenerational transmission reported here also provides further confirmation of the high heritability of autism that is unaccounted for by the contribution of de novo mutations currently emphasized in the field of autism genetics. En ligne : http://dx.doi.org/10.1186/1866-1955-5-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Autism and the broad autism phenotype: familial patterns and intergenerational transmission [Texte imprimé et/ou numérique] / Noah J. SASSON, Auteur ; K. S. LAM, Auteur ; M. PARLIER, Auteur ; Julie L. DANIELS, Auteur ; J. PIVEN, Auteur . - p.11. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.11 Index. décimale : PER Périodiques Résumé : BACKGROUND: Features of the Broad Autism Phenotype (BAP) are disproportionately prevalent in parents of a child with autism, highlighting familial patterns indicative of heritability. It is unclear, however, whether the presence of BAP features in both parents confers an increased liability for autism. The current study explores whether the presence of BAP features in two biological parents occurs more frequently in parents of a child with autism relative to comparison parents, whether parental pairs of a child with autism more commonly consist of one or two parents with BAP features, and whether these features are associated with severity of autism behaviors in probands. METHOD: Seven hundred eleven parents of a child with an autism spectrum disorder and 981 comparison parents completed the Broad Autism Phenotype Questionnaire. Parents of a child with autism also completed the Social Communication Questionnaire. RESULTS: Although parental pairs of a child with autism were more likely than comparison parental pairs to have both parents characterized by the presence of the BAP, they more commonly consisted of a single parent with BAP features. The presence of the BAP in parents was associated with the severity of autism behaviors in probands, with the lowest severity occurring for children of parental pairs in which neither parent exhibited a BAP feature. Severity did not differ between children of two affected parents and those of just one. CONCLUSIONS: Collectively, these findings indicate that parental pairs of children with autism frequently consist of a single parent with BAP characteristics and suggest that future studies searching for implicated genes may benefit from a more narrow focus that identifies the transmitting parent. The evidence of intergenerational transmission reported here also provides further confirmation of the high heritability of autism that is unaccounted for by the contribution of de novo mutations currently emphasized in the field of autism genetics. En ligne : http://dx.doi.org/10.1186/1866-1955-5-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees / M. WOODBURY-SMITH in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 20 p. Titre : A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees Type de document : Texte imprimé et/ou numérique Auteurs : M. WOODBURY-SMITH, Auteur ; Andrew D. PATERSON, Auteur ; I. O'CONNOR, Auteur ; M. ZARREI, Auteur ; R. K. C. YUEN, Auteur ; J. L. HOWE, Auteur ; A. THOMPSON, Auteur ; M. PARLIER, Auteur ; B. FERNANDEZ, Auteur ; J. PIVEN, Auteur ; Stephen SCHERER, Auteur ; V. VIELAND, Auteur ; P. SZATMARI, Auteur Année de publication : 2018 Article en page(s) : 20 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Extended pedigrees  Family genetics  Genome-wide linkage  Posterior probability of linkage (PPL) Index. décimale : PER Périodiques Résumé : BACKGROUND: Although several genetic variants for autism spectrum disorder (ASD) have now been identified, these largely occur sporadically or are de novo. Much less progress has been made in identifying inherited variants, even though the disorder itself is familial in the majority of cases. The objective of this study was to identify chromosomal regions that harbor inherited variants increasing the risk for ASD using an approach that examined both ASD and the broad autism phenotype (BAP) among a unique sample of extended pedigrees. METHODS: ASD and BAP were assessed using standardized tools in 28 pedigrees from Canada and the USA, each with at least three ASD-diagnosed individuals from two nuclear families. Genome-wide linkage analysis was performed using the posterior probability of linkage (PPL) statistic, a quasi-Bayesian method that provides strength of evidence for or against linkage in an essentially model-free manner, with outcomes on the probability scale. RESULTS: The results confirm appreciable interfamilial heterogeneity as well as a high level of intrafamilial heterogeneity. Both ASD and combined ASD/BAP specific loci are apparent. CONCLUSIONS: Inclusion of subclinical phenotypes such as BAP should be more widely employed in genetic studies of ASD as a way of identifying inherited genetic variants for the disorder. Moreover, the results underscore the need for approaches to identifying genetic risk factors in extended pedigrees that are robust to high levels of inter/intrafamilial locus and allelic heterogeneity. En ligne : http://dx.doi.org/10.1186/s11689-018-9238-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees [Texte imprimé et/ou numérique] / M. WOODBURY-SMITH, Auteur ; Andrew D. PATERSON, Auteur ; I. O'CONNOR, Auteur ; M. ZARREI, Auteur ; R. K. C. YUEN, Auteur ; J. L. HOWE, Auteur ; A. THOMPSON, Auteur ; M. PARLIER, Auteur ; B. FERNANDEZ, Auteur ; J. PIVEN, Auteur ; Stephen SCHERER, Auteur ; V. VIELAND, Auteur ; P. SZATMARI, Auteur . - 2018 . - 20 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 20 p. Mots-clés : Autism spectrum disorder (ASD)  Extended pedigrees  Family genetics  Genome-wide linkage  Posterior probability of linkage (PPL) Index. décimale : PER Périodiques Résumé : BACKGROUND: Although several genetic variants for autism spectrum disorder (ASD) have now been identified, these largely occur sporadically or are de novo. Much less progress has been made in identifying inherited variants, even though the disorder itself is familial in the majority of cases. The objective of this study was to identify chromosomal regions that harbor inherited variants increasing the risk for ASD using an approach that examined both ASD and the broad autism phenotype (BAP) among a unique sample of extended pedigrees. METHODS: ASD and BAP were assessed using standardized tools in 28 pedigrees from Canada and the USA, each with at least three ASD-diagnosed individuals from two nuclear families. Genome-wide linkage analysis was performed using the posterior probability of linkage (PPL) statistic, a quasi-Bayesian method that provides strength of evidence for or against linkage in an essentially model-free manner, with outcomes on the probability scale. RESULTS: The results confirm appreciable interfamilial heterogeneity as well as a high level of intrafamilial heterogeneity. Both ASD and combined ASD/BAP specific loci are apparent. CONCLUSIONS: Inclusion of subclinical phenotypes such as BAP should be more widely employed in genetic studies of ASD as a way of identifying inherited genetic variants for the disorder. Moreover, the results underscore the need for approaches to identifying genetic risk factors in extended pedigrees that are robust to high levels of inter/intrafamilial locus and allelic heterogeneity. En ligne : http://dx.doi.org/10.1186/s11689-018-9238-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

High rates of parkinsonism in adults with autism / S. STARKSTEIN in Journal of Neurodevelopmental Disorders, 7-1 (December 2015)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.29 Titre : High rates of parkinsonism in adults with autism Type de document : Texte imprimé et/ou numérique Auteurs : S. STARKSTEIN, Auteur ; S. GELLAR, Auteur ; M. PARLIER, Auteur ; L. PAYNE, Auteur ; J. PIVEN, Auteur Article en page(s) : p.29 Langues : Anglais (eng) Mots-clés : adults  autism  movement disorders  parkinsonism  parkinson's disease Index. décimale : PER Périodiques Résumé : BACKGROUND: While it is now recognized that autism spectrum disorder (ASD) is typically a life-long condition, there exist only a handful of systematic studies on middle-aged and older adults with this condition. METHODS: We first performed a structured examination of parkinsonian motor signs in a hypothesis-generating, pilot study (study I) of 19 adults with ASD over 49 years of age. Observing high rates of parkinsonism in those off atypical neuroleptics (2/12, 17 %) in comparison to published population rates for Parkinson's disease and parkinsonism, we examined a second sample of 37 adults with ASD, over 39 years of age, using a structured neurological assessment for parkinsonism. RESULTS: Twelve of the 37 subjects (32 %) met the diagnostic criteria for parkinsonism; however, of these, 29 subjects were on atypical neuroleptics, complicating interpretation of the findings. Two of eight (25 %) subjects not taking atypical neuroleptic medications met the criteria for parkinsonism. Combining subjects who were not currently taking atypical neuroleptic medications, across both studies, we conservatively classified 4/20 (20 %) with parkinsonism. CONCLUSIONS: We find a high frequency of parkinsonism among ASD individuals older than 39 years. If high rates of parkinsonism and potentially Parkinson's disease are confirmed in subsequent studies of ASD, this observation has important implications for understanding the neurobiology of autism and treatment of manifestations in older adults. Given the prevalence of autism in school-age children, the recognition of its life-long natural history, and the recognition of the aging of western societies, these findings also support the importance of further systematic study of other aspects of older adults with autism. En ligne : http://dx.doi.org/10.1186/s11689-015-9125-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] High rates of parkinsonism in adults with autism [Texte imprimé et/ou numérique] / S. STARKSTEIN, Auteur ; S. GELLAR, Auteur ; M. PARLIER, Auteur ; L. PAYNE, Auteur ; J. PIVEN, Auteur . - p.29. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.29 Mots-clés : adults  autism  movement disorders  parkinsonism  parkinson's disease Index. décimale : PER Périodiques Résumé : BACKGROUND: While it is now recognized that autism spectrum disorder (ASD) is typically a life-long condition, there exist only a handful of systematic studies on middle-aged and older adults with this condition. METHODS: We first performed a structured examination of parkinsonian motor signs in a hypothesis-generating, pilot study (study I) of 19 adults with ASD over 49 years of age. Observing high rates of parkinsonism in those off atypical neuroleptics (2/12, 17 %) in comparison to published population rates for Parkinson's disease and parkinsonism, we examined a second sample of 37 adults with ASD, over 39 years of age, using a structured neurological assessment for parkinsonism. RESULTS: Twelve of the 37 subjects (32 %) met the diagnostic criteria for parkinsonism; however, of these, 29 subjects were on atypical neuroleptics, complicating interpretation of the findings. Two of eight (25 %) subjects not taking atypical neuroleptic medications met the criteria for parkinsonism. Combining subjects who were not currently taking atypical neuroleptic medications, across both studies, we conservatively classified 4/20 (20 %) with parkinsonism. CONCLUSIONS: We find a high frequency of parkinsonism among ASD individuals older than 39 years. If high rates of parkinsonism and potentially Parkinson's disease are confirmed in subsequent studies of ASD, this observation has important implications for understanding the neurobiology of autism and treatment of manifestations in older adults. Given the prevalence of autism in school-age children, the recognition of its life-long natural history, and the recognition of the aging of western societies, these findings also support the importance of further systematic study of other aspects of older adults with autism. En ligne : http://dx.doi.org/10.1186/s11689-015-9125-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

A molecular genetic study of autism and related phenotypes in extended pedigrees / J. PIVEN in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.30 Titre : A molecular genetic study of autism and related phenotypes in extended pedigrees Type de document : Texte imprimé et/ou numérique Auteurs : J. PIVEN, Auteur ; V. J. VIELAND, Auteur ; M. PARLIER, Auteur ; A. THOMPSON, Auteur ; I. O'CONNER, Auteur ; M. WOODBURY-SMITH, Auteur ; Y. HUANG, Auteur ; K. A. WALTERS, Auteur ; B. FERNANDEZ, Auteur ; P. SZATMARI, Auteur Article en page(s) : p.30 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. METHODS: We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. RESULTS: Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior', showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. CONCLUSIONS: These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears to correspond to sets of subclinical features segregating with ASD within pedigrees, and that different features of the ASD phenotype segregate independently of one another. These findings support the additional study of larger, even more individually informative pedigrees, together with measurement of multiple, behavioral- and biomarker-based phenotypes, in both affected and non-affected individuals, to elucidate the complex genetics of familial ASD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-30 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] A molecular genetic study of autism and related phenotypes in extended pedigrees [Texte imprimé et/ou numérique] / J. PIVEN, Auteur ; V. J. VIELAND, Auteur ; M. PARLIER, Auteur ; A. THOMPSON, Auteur ; I. O'CONNER, Auteur ; M. WOODBURY-SMITH, Auteur ; Y. HUANG, Auteur ; K. A. WALTERS, Auteur ; B. FERNANDEZ, Auteur ; P. SZATMARI, Auteur . - p.30. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.30 Index. décimale : PER Périodiques Résumé : BACKGROUND: Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. METHODS: We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. RESULTS: Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior', showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. CONCLUSIONS: These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears to correspond to sets of subclinical features segregating with ASD within pedigrees, and that different features of the ASD phenotype segregate independently of one another. These findings support the additional study of larger, even more individually informative pedigrees, together with measurement of multiple, behavioral- and biomarker-based phenotypes, in both affected and non-affected individuals, to elucidate the complex genetics of familial ASD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-30 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Prevalence of selected clinical problems in older adults with autism and intellectual disability / D. KATS in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.27 Titre : Prevalence of selected clinical problems in older adults with autism and intellectual disability Type de document : Texte imprimé et/ou numérique Auteurs : D. KATS, Auteur ; L. PAYNE, Auteur ; M. PARLIER, Auteur ; J. PIVEN, Auteur Article en page(s) : p.27 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Originally described as a disorder of childhood, evidence now demonstrates the lifelong nature of autism spectrum disorder (ASD). Despite the increase of the population over age 65, older adults with ASD remain a scarcely explored subpopulation. This study set out to investigate the prevalence of clinically relevant behaviors and medical problems in a sample of US adults aged 30 to 59 with ASD and intellectual disability (ID), in comparison to those with ID only. METHODS: A cross-sectional study, with both an exploratory and replication analysis, was conducted using National Core Indicators (NCI) multi-state surveys from 2009 to 2010 and 2010 to 2011. There were 4,989 and 4,261 adults aged 30-59 with ID examined from the 2009 to 2010 and 2010 to 2011 samples, respectively. The two consecutive annual samples consisted of 438 (9%) and 298 (7%) individuals with ASD and ID. Variables were chosen from the NCI data as outcomes, including medication use for behavior problems, severe or aggressive behavior problems and selected medical conditions. RESULTS: No age-associated disparities were observed between adults with ASD and ID versus adults with ID only in either sample. For the 2009 to 2010 sample, the prevalence of support needed to manage self-injurious, disruptive and destructive behavior in subjects with ASD and ID ranged from 40 to 60%. Similarly, the prevalence estimates of self-injurious, disruptive and destructive behavior were each almost double in adults with ASD and ID relative to those with ID only. These results were replicated in the 2010 to 2011 sample. CONCLUSIONS: The findings of this study highlight the urgent need for research on the nature and treatment of severe behavior problems in the rapidly increasing population of older adults with ASD. They also suggest the importance of developing policies that expand our capacity to care for these individuals. En ligne : http://dx.doi.org/10.1186/1866-1955-5-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Prevalence of selected clinical problems in older adults with autism and intellectual disability [Texte imprimé et/ou numérique] / D. KATS, Auteur ; L. PAYNE, Auteur ; M. PARLIER, Auteur ; J. PIVEN, Auteur . - p.27. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.27 Index. décimale : PER Périodiques Résumé : BACKGROUND: Originally described as a disorder of childhood, evidence now demonstrates the lifelong nature of autism spectrum disorder (ASD). Despite the increase of the population over age 65, older adults with ASD remain a scarcely explored subpopulation. This study set out to investigate the prevalence of clinically relevant behaviors and medical problems in a sample of US adults aged 30 to 59 with ASD and intellectual disability (ID), in comparison to those with ID only. METHODS: A cross-sectional study, with both an exploratory and replication analysis, was conducted using National Core Indicators (NCI) multi-state surveys from 2009 to 2010 and 2010 to 2011. There were 4,989 and 4,261 adults aged 30-59 with ID examined from the 2009 to 2010 and 2010 to 2011 samples, respectively. The two consecutive annual samples consisted of 438 (9%) and 298 (7%) individuals with ASD and ID. Variables were chosen from the NCI data as outcomes, including medication use for behavior problems, severe or aggressive behavior problems and selected medical conditions. RESULTS: No age-associated disparities were observed between adults with ASD and ID versus adults with ID only in either sample. For the 2009 to 2010 sample, the prevalence of support needed to manage self-injurious, disruptive and destructive behavior in subjects with ASD and ID ranged from 40 to 60%. Similarly, the prevalence estimates of self-injurious, disruptive and destructive behavior were each almost double in adults with ASD and ID relative to those with ID only. These results were replicated in the 2010 to 2011 sample. CONCLUSIONS: The findings of this study highlight the urgent need for research on the nature and treatment of severe behavior problems in the rapidly increasing population of older adults with ASD. They also suggest the importance of developing policies that expand our capacity to care for these individuals. En ligne : http://dx.doi.org/10.1186/1866-1955-5-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

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