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

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

Modulation of mu attenuation to social stimuli in children and adults with 16p11.2 deletions and duplications / C. M. HUDAC in Journal of Neurodevelopmental Disorders, 7-1 (December 2015)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.25 Titre : Modulation of mu attenuation to social stimuli in children and adults with 16p11.2 deletions and duplications Type de document : Texte imprimé et/ou numérique Auteurs : C. M. HUDAC, Auteur ; A. KRESSE, Auteur ; Benjamin AARONSON, Auteur ; Trent D. DESCHAMPS, Auteur ; S. J. WEBB, Auteur ; Raphael BERNIER, Auteur Article en page(s) : p.25 Langues : Anglais (eng) Mots-clés : 16p11.2  Autism spectrum disorder (ASD)  Copy number variation (CNV)  Electroencephalogram (EEG)  Molecular subtyping  Mu attenuation  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Copy number variations (CNV) within the recurrent ~600 kb chromosomal locus of 16p11.2 are associated with a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, little is known about the social brain phenotype of 16p11.2 CNV and how this phenotype is related to the social impairments associated with CNVs at this locus. The aim of this preliminary study was to use molecular subtyping to establish the social brain phenotype of individuals with 16p11.2 CNV and how these patterns relate to typical development and ASD. METHODS: We evaluated the social brain phenotype as expressed by mu attenuation in 48 children and adults characterized as duplication carriers (n = 12), deletion carriers (n = 12), individuals with idiopathic ASD (n = 8), and neurotypical controls (n = 16). Participants watched videos containing social and nonsocial motion during electroencephalogram (EEG) acquisition. RESULTS: Overall, only the typical group exhibited predicted patterns of mu modulation to social information (e.g., greater mu attenuation for social than nonsocial motion). Both 16p11.2 CNV groups exhibited more mu attenuation for nonsocial than social motion. The ASD group did not discriminate between conditions and demonstrated less mu attenuation compared to the typical and duplication carriers. Single-trial analysis indicated that mu attenuation decreased over time more rapidly for 16p11.2 CNV groups than the typical group. The duplication group did not diverge from typical patterns of mu attenuation until after initial exposure. CONCLUSIONS: These results indicate atypical but unique patterns of mu attenuation for deletion and duplication carriers, highlighting the need to continue characterizing the social brain phenotype associated with 16p11.2 CNVs. En ligne : http://dx.doi.org/10.1186/s11689-015-9118-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347 [article] Modulation of mu attenuation to social stimuli in children and adults with 16p11.2 deletions and duplications [Texte imprimé et/ou numérique] / C. M. HUDAC, Auteur ; A. KRESSE, Auteur ; Benjamin AARONSON, Auteur ; Trent D. DESCHAMPS, Auteur ; S. J. WEBB, Auteur ; Raphael BERNIER, Auteur . - p.25. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.25 Mots-clés : 16p11.2  Autism spectrum disorder (ASD)  Copy number variation (CNV)  Electroencephalogram (EEG)  Molecular subtyping  Mu attenuation  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Copy number variations (CNV) within the recurrent ~600 kb chromosomal locus of 16p11.2 are associated with a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, little is known about the social brain phenotype of 16p11.2 CNV and how this phenotype is related to the social impairments associated with CNVs at this locus. The aim of this preliminary study was to use molecular subtyping to establish the social brain phenotype of individuals with 16p11.2 CNV and how these patterns relate to typical development and ASD. METHODS: We evaluated the social brain phenotype as expressed by mu attenuation in 48 children and adults characterized as duplication carriers (n = 12), deletion carriers (n = 12), individuals with idiopathic ASD (n = 8), and neurotypical controls (n = 16). Participants watched videos containing social and nonsocial motion during electroencephalogram (EEG) acquisition. RESULTS: Overall, only the typical group exhibited predicted patterns of mu modulation to social information (e.g., greater mu attenuation for social than nonsocial motion). Both 16p11.2 CNV groups exhibited more mu attenuation for nonsocial than social motion. The ASD group did not discriminate between conditions and demonstrated less mu attenuation compared to the typical and duplication carriers. Single-trial analysis indicated that mu attenuation decreased over time more rapidly for 16p11.2 CNV groups than the typical group. The duplication group did not diverge from typical patterns of mu attenuation until after initial exposure. CONCLUSIONS: These results indicate atypical but unique patterns of mu attenuation for deletion and duplication carriers, highlighting the need to continue characterizing the social brain phenotype associated with 16p11.2 CNVs. En ligne : http://dx.doi.org/10.1186/s11689-015-9118-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347

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