Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism / K. LUHRS in Autism Research and Treatment, 2017 (2017)  

Public ISBD [article]  inAutism Research and Treatment > 2017 (2017) Titre : Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism Type de document : Texte imprimé et/ou numérique Auteurs : K. LUHRS, Auteur ; T. WARD, Auteur ; C. M. HUDAC, Auteur ; J. GERDTS, Auteur ; H. A. F. STESSMAN, Auteur ; E. E. EICHLER, Auteur ; Raphael BERNIER, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The purpose of this study was to examine the confluence of genetic and familial risk factors in children with Autism Spectrum Disorder (ASD) with distinct de novo genetic events. We hypothesized that gene-disrupting mutations would be associated with reduced rates of familial psychiatric disorders relative to structural mutations. Participants included families of children with ASD in four groups: de novo duplication copy number variations (DUP, n = 62), de novo deletion copy number variations (DEL, n = 74), de novo likely gene-disrupting mutations (LGDM, n = 267), and children without a known genetic etiology (NON, n = 2111). Familial rates of psychiatric disorders were calculated from semistructured interviews. Results indicated overall increased rates of psychiatric disorders in DUP families compared to DEL and LGDM families, specific to paternal psychiatric histories, and particularly evident for depressive disorders. Higher rates of depressive disorders in maternal psychiatric histories were observed overall compared to paternal histories and higher rates of anxiety disorders were observed in paternal histories for LGDM families compared to DUP families. These findings support the notion of an additive contribution of genetic etiology and familial factors are associated with ASD risk and highlight critical need for continued work targeting these relationships. En ligne : http://dx.doi.org/10.1155/2017/9371964 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=333 [article] Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism [Texte imprimé et/ou numérique] / K. LUHRS, Auteur ; T. WARD, Auteur ; C. M. HUDAC, Auteur ; J. GERDTS, Auteur ; H. A. F. STESSMAN, Auteur ; E. E. EICHLER, Auteur ; Raphael BERNIER, Auteur. Langues : Anglais (eng) in Autism Research and Treatment > 2017 (2017) Index. décimale : PER Périodiques Résumé : The purpose of this study was to examine the confluence of genetic and familial risk factors in children with Autism Spectrum Disorder (ASD) with distinct de novo genetic events. We hypothesized that gene-disrupting mutations would be associated with reduced rates of familial psychiatric disorders relative to structural mutations. Participants included families of children with ASD in four groups: de novo duplication copy number variations (DUP, n = 62), de novo deletion copy number variations (DEL, n = 74), de novo likely gene-disrupting mutations (LGDM, n = 267), and children without a known genetic etiology (NON, n = 2111). Familial rates of psychiatric disorders were calculated from semistructured interviews. Results indicated overall increased rates of psychiatric disorders in DUP families compared to DEL and LGDM families, specific to paternal psychiatric histories, and particularly evident for depressive disorders. Higher rates of depressive disorders in maternal psychiatric histories were observed overall compared to paternal histories and higher rates of anxiety disorders were observed in paternal histories for LGDM families compared to DUP families. These findings support the notion of an additive contribution of genetic etiology and familial factors are associated with ASD risk and highlight critical need for continued work targeting these relationships. En ligne : http://dx.doi.org/10.1155/2017/9371964 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=333

Brief Report: Associations Between Self-injurious Behaviors and Abdominal Pain Among Individuals with ASD-Associated Disruptive Mutations / E. C. KURTZ-NELSON in Journal of Autism and Developmental Disorders, 51-9 (September 2021)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 51-9 (September 2021) . - p.3365-3373 Titre : Brief Report: Associations Between Self-injurious Behaviors and Abdominal Pain Among Individuals with ASD-Associated Disruptive Mutations Type de document : Texte imprimé et/ou numérique Auteurs : E. C. KURTZ-NELSON, Auteur ; S. W. THAM, Auteur ; K. AHLERS, Auteur ; D. CHO, Auteur ; Arianne S. WALLACE, Auteur ; E. E. EICHLER, Auteur ; Raphael BERNIER, Auteur ; R. K. EARL, Auteur Article en page(s) : p.3365-3373 Langues : Anglais (eng) Mots-clés : Abdominal Pain/genetics  Autism Spectrum Disorder/epidemiology/genetics  Humans  Mutation  Risk Factors  Self-Injurious Behavior/epidemiology/genetics  Abdominal pain  Autism spectrum disorder  Intellectual disability  Rare genetic disorders  Self-injurious behavior  Inc. The remaining authors have no conflicts of interest to report. Index. décimale : PER Périodiques Résumé : Self-injurious behaviors (SIB) are elevated in autism spectrum disorder (ASD) and related genetic disorders, but the genetic and biological mechanisms that contribute to SIB in ASD are poorly understood. This study examined rates and predictors of SIB in 112 individuals with disruptive mutations to ASD-risk genes. Current SIB were reported in 30% of participants and associated with poorer cognitive and adaptive skills. History of severe abdominal pain predicted higher rates of SIB and SIB severity after controlling for age and adaptive behavior; individuals with a history of severe abdominal pain were eight times more likely to exhibit SIB than those with no history. Future research is needed to examine associations between genetic risk, pain, and SIB in this population. En ligne : http://dx.doi.org/10.1007/s10803-020-04774-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453 [article] Brief Report: Associations Between Self-injurious Behaviors and Abdominal Pain Among Individuals with ASD-Associated Disruptive Mutations [Texte imprimé et/ou numérique] / E. C. KURTZ-NELSON, Auteur ; S. W. THAM, Auteur ; K. AHLERS, Auteur ; D. CHO, Auteur ; Arianne S. WALLACE, Auteur ; E. E. EICHLER, Auteur ; Raphael BERNIER, Auteur ; R. K. EARL, Auteur . - p.3365-3373. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 51-9 (September 2021) . - p.3365-3373 Mots-clés : Abdominal Pain/genetics  Autism Spectrum Disorder/epidemiology/genetics  Humans  Mutation  Risk Factors  Self-Injurious Behavior/epidemiology/genetics  Abdominal pain  Autism spectrum disorder  Intellectual disability  Rare genetic disorders  Self-injurious behavior  Inc. The remaining authors have no conflicts of interest to report. Index. décimale : PER Périodiques Résumé : Self-injurious behaviors (SIB) are elevated in autism spectrum disorder (ASD) and related genetic disorders, but the genetic and biological mechanisms that contribute to SIB in ASD are poorly understood. This study examined rates and predictors of SIB in 112 individuals with disruptive mutations to ASD-risk genes. Current SIB were reported in 30% of participants and associated with poorer cognitive and adaptive skills. History of severe abdominal pain predicted higher rates of SIB and SIB severity after controlling for age and adaptive behavior; individuals with a history of severe abdominal pain were eight times more likely to exhibit SIB than those with no history. Future research is needed to examine associations between genetic risk, pain, and SIB in this population. En ligne : http://dx.doi.org/10.1007/s10803-020-04774-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453

Clinical phenotype of ASD-associated DYRK1A haploinsufficiency / R. K. EARL in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 54p. Titre : Clinical phenotype of ASD-associated DYRK1A haploinsufficiency Type de document : Texte imprimé et/ou numérique Auteurs : R. K. EARL, Auteur ; Tychele N. TURNER, Auteur ; H. C. MEFFORD, Auteur ; C. M. HUDAC, Auteur ; J. GERDTS, Auteur ; E. E. EICHLER, Auteur ; Raphael BERNIER, Auteur Article en page(s) : 54p. Langues : Anglais (eng) Mots-clés : Autism  Clinical phenotype  Dyrk1a  Disruptive mutation  Genetic syndrome  Genetically defined subtype Index. décimale : PER Périodiques Résumé : BACKGROUND: DYRK1A is a gene recurrently disrupted in 0.1-0.5% of the ASD population. A growing number of case reports with DYRK1A haploinsufficiency exhibit common phenotypic features including microcephaly, intellectual disability, speech delay, and facial dysmorphisms. METHODS: Phenotypic information from previously published DYRK1A cases (n = 51) and participants in an ongoing study at the University of Washington (UW, n = 10) were compiled. Frequencies of recurrent phenotypic features in this population were compared to features observed in a large sample with idiopathic ASD from the Simons Simplex Collection (n = 1981). UW DYRK1A cases were further characterized quantitatively and compared to a randomly subsampled set of idiopathic ASD cases matched on age and gender (n = 10) and to cases with an ASD-associated disruptive mutation to CHD8 (n = 12). Contribution of familial genetic background to clinical heterogeneity was assessed by comparing head circumference, IQ, and ASD-related symptoms of UW DYRK1A cases to their unaffected parents. RESULTS: DYRK1A haploinsufficiency results in a common phenotypic profile including intellectual disability, speech and motor difficulties, microcephaly, feeding difficulties, and vision abnormalities. Eighty-nine percent of DYRK1A cases ascertained for ASD presented with a constellation of five or more of these symptoms. When compared quantitatively, DYRK1A cases presented with significantly lower IQ and adaptive functioning compared to idiopathic cases and significantly smaller head size compared to both idiopathic and CHD8 cases. Phenotypic variability in parental head circumference, IQ, and ASD-related symptoms corresponded to observed variability in affected child phenotype. CONCLUSIONS: Results confirm a core clinical phenotype for DYRK1A disruptions, with a combination of features that is distinct from idiopathic ASD. Cases with DYRK1A mutations are also distinguishable from disruptive mutations to CHD8 by head size. Measurable, quantitative characterization of DYRK1A haploinsufficiency illuminates clinical variability, which may be, in part, due to familial genetic background. En ligne : http://dx.doi.org/10.1186/s13229-017-0173-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Clinical phenotype of ASD-associated DYRK1A haploinsufficiency [Texte imprimé et/ou numérique] / R. K. EARL, Auteur ; Tychele N. TURNER, Auteur ; H. C. MEFFORD, Auteur ; C. M. HUDAC, Auteur ; J. GERDTS, Auteur ; E. E. EICHLER, Auteur ; Raphael BERNIER, Auteur . - 54p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 54p. Mots-clés : Autism  Clinical phenotype  Dyrk1a  Disruptive mutation  Genetic syndrome  Genetically defined subtype Index. décimale : PER Périodiques Résumé : BACKGROUND: DYRK1A is a gene recurrently disrupted in 0.1-0.5% of the ASD population. A growing number of case reports with DYRK1A haploinsufficiency exhibit common phenotypic features including microcephaly, intellectual disability, speech delay, and facial dysmorphisms. METHODS: Phenotypic information from previously published DYRK1A cases (n = 51) and participants in an ongoing study at the University of Washington (UW, n = 10) were compiled. Frequencies of recurrent phenotypic features in this population were compared to features observed in a large sample with idiopathic ASD from the Simons Simplex Collection (n = 1981). UW DYRK1A cases were further characterized quantitatively and compared to a randomly subsampled set of idiopathic ASD cases matched on age and gender (n = 10) and to cases with an ASD-associated disruptive mutation to CHD8 (n = 12). Contribution of familial genetic background to clinical heterogeneity was assessed by comparing head circumference, IQ, and ASD-related symptoms of UW DYRK1A cases to their unaffected parents. RESULTS: DYRK1A haploinsufficiency results in a common phenotypic profile including intellectual disability, speech and motor difficulties, microcephaly, feeding difficulties, and vision abnormalities. Eighty-nine percent of DYRK1A cases ascertained for ASD presented with a constellation of five or more of these symptoms. When compared quantitatively, DYRK1A cases presented with significantly lower IQ and adaptive functioning compared to idiopathic cases and significantly smaller head size compared to both idiopathic and CHD8 cases. Phenotypic variability in parental head circumference, IQ, and ASD-related symptoms corresponded to observed variability in affected child phenotype. CONCLUSIONS: Results confirm a core clinical phenotype for DYRK1A disruptions, with a combination of features that is distinct from idiopathic ASD. Cases with DYRK1A mutations are also distinguishable from disruptive mutations to CHD8 by head size. Measurable, quantitative characterization of DYRK1A haploinsufficiency illuminates clinical variability, which may be, in part, due to familial genetic background. En ligne : http://dx.doi.org/10.1186/s13229-017-0173-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

Exploring the heterogeneity of neural social indices for genetically distinct etiologies of autism / C. M. HUDAC in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.24 Titre : Exploring the heterogeneity of neural social indices for genetically distinct etiologies of autism Type de document : Texte imprimé et/ou numérique Auteurs : C. M. HUDAC, Auteur ; H. A. F. STESSMAN, Auteur ; Trent D. DESCHAMPS, Auteur ; A. KRESSE, Auteur ; S. FAJA, Auteur ; E. NEUHAUS, Auteur ; S. J. WEBB, Auteur ; E. E. EICHLER, Auteur ; Raphael BERNIER, Auteur Article en page(s) : p.24 Langues : Anglais (eng) Mots-clés : Autism spectrum disorders (ASD)  Electroencephalography (EEG)  Likely gene-disrupting mutations  Molecular subtyping  Mu rhythm attenuation  Social cognition  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous disorder. Promising initiatives utilizing interdisciplinary characterization of ASD suggest phenotypic subtypes related to specific likely gene-disrupting mutations (LGDMs). However, the role of functionally associated LGDMs in the neural social phenotype is unknown. METHODS: In this study of 26 children with ASD (n = 13 with an LGDM) and 13 control children, we characterized patterns of mu attenuation and habituation as children watched videos containing social and nonsocial motions during electroencephalography acquisition. RESULTS: Diagnostic comparisons were consistent with prior work suggesting aberrant mu attenuation in ASD within the upper mu band (10-12 Hz), but typical patterns within the lower mu band (8-10 Hz). Preliminary exploration indicated distinct social sensitization patterns (i.e., increasing mu attenuation for social motion) for children with an LGDM that is primarily expressed during embryonic development. In contrast, children with an LGDM primarily expressed post-embryonic development exhibited stable typical patterns of lower mu attenuation. Neural social indices were associated with social responsiveness, but not cognition. CONCLUSIONS: These findings suggest unique neurophysiological profiles for certain genetic etiologies of ASD, further clarifying possible genetic functional subtypes of ASD and providing insight into mechanisms for targeted treatment approaches. En ligne : http://dx.doi.org/10.1186/s11689-017-9199-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Exploring the heterogeneity of neural social indices for genetically distinct etiologies of autism [Texte imprimé et/ou numérique] / C. M. HUDAC, Auteur ; H. A. F. STESSMAN, Auteur ; Trent D. DESCHAMPS, Auteur ; A. KRESSE, Auteur ; S. FAJA, Auteur ; E. NEUHAUS, Auteur ; S. J. WEBB, Auteur ; E. E. EICHLER, Auteur ; Raphael BERNIER, Auteur . - p.24. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.24 Mots-clés : Autism spectrum disorders (ASD)  Electroencephalography (EEG)  Likely gene-disrupting mutations  Molecular subtyping  Mu rhythm attenuation  Social cognition  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous disorder. Promising initiatives utilizing interdisciplinary characterization of ASD suggest phenotypic subtypes related to specific likely gene-disrupting mutations (LGDMs). However, the role of functionally associated LGDMs in the neural social phenotype is unknown. METHODS: In this study of 26 children with ASD (n = 13 with an LGDM) and 13 control children, we characterized patterns of mu attenuation and habituation as children watched videos containing social and nonsocial motions during electroencephalography acquisition. RESULTS: Diagnostic comparisons were consistent with prior work suggesting aberrant mu attenuation in ASD within the upper mu band (10-12 Hz), but typical patterns within the lower mu band (8-10 Hz). Preliminary exploration indicated distinct social sensitization patterns (i.e., increasing mu attenuation for social motion) for children with an LGDM that is primarily expressed during embryonic development. In contrast, children with an LGDM primarily expressed post-embryonic development exhibited stable typical patterns of lower mu attenuation. Neural social indices were associated with social responsiveness, but not cognition. CONCLUSIONS: These findings suggest unique neurophysiological profiles for certain genetic etiologies of ASD, further clarifying possible genetic functional subtypes of ASD and providing insight into mechanisms for targeted treatment approaches. En ligne : http://dx.doi.org/10.1186/s11689-017-9199-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Genomic studies in fragile X premutation carriers / R. LOZANO in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.27 Titre : Genomic studies in fragile X premutation carriers Type de document : Texte imprimé et/ou numérique Auteurs : R. LOZANO, Auteur ; Randi J. HAGERMAN, Auteur ; M. DUYZEND, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; E. E. EICHLER, Auteur ; F. TASSONE, Auteur Article en page(s) : p.27 Langues : Anglais (eng) Mots-clés : Asd  Autism  FMR1 gene  Neurodevelopmental disorders  Neurological disorders  Premutation  Second hit Index. décimale : PER Périodiques Résumé : BACKGROUND: The FMR1 premutation is defined as having 55 to 200 CGG repeats in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1). The clinical involvement has been well characterized for fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). The behavior/psychiatric and other neurological manifestations remain to be specified as well as the molecular mechanisms that will explain the phenotypic variability observed in individuals with the FMR1 premutation. METHODS: Here we describe a small pilot study of copy number variants (CNVs) in 56 participants with a premutation ranging from 55 to 192 repeats. The participants were divided into four different clinical groups for the analysis: those with behavioral problems but no autism spectrum disorder (ASD); those with ASD but without neurological problems; those with ASD and neurological problems including seizures; and those with neurological problems without ASD. RESULTS: We found 12 rare CNVs (eight duplications and four deletions) in 11 cases (19.6%) that were not found in approximately 8,000 controls. Three of them were at 10q26 and two at Xp22.3, with small areas of overlap. The CNVs were more commonly identified in individuals with neurological involvement and ASD. CONCLUSIONS: The frequencies were not statistically significant across the groups. There were no significant differences in the psychometric and behavior scores among all groups. Further studies are necessary to determine the frequency of second genetic hits in individuals with the FMR1 premutation; however, these preliminary results suggest that genomic studies can be useful in understanding the molecular etiology of clinical involvement in premutation carriers with ASD and neurological involvement. En ligne : http://dx.doi.org/10.1186/1866-1955-6-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346 [article] Genomic studies in fragile X premutation carriers [Texte imprimé et/ou numérique] / R. LOZANO, Auteur ; Randi J. HAGERMAN, Auteur ; M. DUYZEND, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; E. E. EICHLER, Auteur ; F. TASSONE, Auteur . - p.27. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.27 Mots-clés : Asd  Autism  FMR1 gene  Neurodevelopmental disorders  Neurological disorders  Premutation  Second hit Index. décimale : PER Périodiques Résumé : BACKGROUND: The FMR1 premutation is defined as having 55 to 200 CGG repeats in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1). The clinical involvement has been well characterized for fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). The behavior/psychiatric and other neurological manifestations remain to be specified as well as the molecular mechanisms that will explain the phenotypic variability observed in individuals with the FMR1 premutation. METHODS: Here we describe a small pilot study of copy number variants (CNVs) in 56 participants with a premutation ranging from 55 to 192 repeats. The participants were divided into four different clinical groups for the analysis: those with behavioral problems but no autism spectrum disorder (ASD); those with ASD but without neurological problems; those with ASD and neurological problems including seizures; and those with neurological problems without ASD. RESULTS: We found 12 rare CNVs (eight duplications and four deletions) in 11 cases (19.6%) that were not found in approximately 8,000 controls. Three of them were at 10q26 and two at Xp22.3, with small areas of overlap. The CNVs were more commonly identified in individuals with neurological involvement and ASD. CONCLUSIONS: The frequencies were not statistically significant across the groups. There were no significant differences in the psychometric and behavior scores among all groups. Further studies are necessary to determine the frequency of second genetic hits in individuals with the FMR1 premutation; however, these preliminary results suggest that genomic studies can be useful in understanding the molecular etiology of clinical involvement in premutation carriers with ASD and neurological involvement. En ligne : http://dx.doi.org/10.1186/1866-1955-6-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346

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

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Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications / J. A. ROSENFELD in Journal of Neurodevelopmental Disorders, 2-1 (March 2010)  

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The autism spectrum phenotype in ADNP syndrome / Anne B. ARNETT in Autism Research, 11-9 (September 2018)  

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