Dépouillements

Male predominance in autism: neuroendocrine influences on arousal and social anxiety / Donald W. PFAFF in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.163-176 Titre : Male predominance in autism: neuroendocrine influences on arousal and social anxiety Type de document : Texte imprimé et/ou numérique Auteurs : Donald W. PFAFF, Auteur ; Isabelle RAPIN, Auteur ; Sylvie GOLDMAN, Auteur Année de publication : 2011 Article en page(s) : p.163-176 Langues : Anglais (eng) Mots-clés : behavioral analysis of animal models  developmental neurobiology  sex differences  testosterone  androgen receptor Index. décimale : PER Périodiques Résumé : We offer a neurobiologic theory based on animal work that helps account for the conspicuous male predominance in autism spectrum disorders (ASD). In young male animals, testosterone (TST) binds to androgen receptors (AR) in brainstem neurons responsible for enhancing brain arousal. As a consequence, arousal-related neurotransmitters bombard the amygdala hypersensitized by TST acting though AR. Arousal-related inputs are known to prime amygdaloid mechanisms for fear and anxiety, with resultant social avoidance. We hypothesize that similar mechanisms contribute to autism's male predominance and to its defining impaired social skills. The theory rests on two key interacting factors: the molecular effects of TST in genetically vulnerable boys in combination with environmental stresses they experienced in utero, neonatally, or during the first years. We postulate that higher TST levels and, therefore, higher amounts of arousal-related inputs to the amygdala sensitize these genetically vulnerable male infants to very early stresses. In sharp contrast to boys, girls not only do not have high levels of TST-facilitated arousal-causing inputs to the amygdala but they also enjoy the protection afforded by estrogenic hormones, oxytocin, and the oxytocin receptor. This theory suggests that novel technologies applied to the molecular endocrinology of TST's actions through AR will offer new avenues of enquiry into ASD. Since the high male preponderance in autism is important yet understudied, we offer our theory, which is based on detailed neurobehavioral research with animals, to stimulate basic and clinical research in animals and humans and hopefully help develop novel more effective medical treatments for autism. En ligne : http://dx.doi.org/10.1002/aur.191 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] Male predominance in autism: neuroendocrine influences on arousal and social anxiety [Texte imprimé et/ou numérique] / Donald W. PFAFF, Auteur ; Isabelle RAPIN, Auteur ; Sylvie GOLDMAN, Auteur . - 2011 . - p.163-176. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.163-176 Mots-clés : behavioral analysis of animal models  developmental neurobiology  sex differences  testosterone  androgen receptor Index. décimale : PER Périodiques Résumé : We offer a neurobiologic theory based on animal work that helps account for the conspicuous male predominance in autism spectrum disorders (ASD). In young male animals, testosterone (TST) binds to androgen receptors (AR) in brainstem neurons responsible for enhancing brain arousal. As a consequence, arousal-related neurotransmitters bombard the amygdala hypersensitized by TST acting though AR. Arousal-related inputs are known to prime amygdaloid mechanisms for fear and anxiety, with resultant social avoidance. We hypothesize that similar mechanisms contribute to autism's male predominance and to its defining impaired social skills. The theory rests on two key interacting factors: the molecular effects of TST in genetically vulnerable boys in combination with environmental stresses they experienced in utero, neonatally, or during the first years. We postulate that higher TST levels and, therefore, higher amounts of arousal-related inputs to the amygdala sensitize these genetically vulnerable male infants to very early stresses. In sharp contrast to boys, girls not only do not have high levels of TST-facilitated arousal-causing inputs to the amygdala but they also enjoy the protection afforded by estrogenic hormones, oxytocin, and the oxytocin receptor. This theory suggests that novel technologies applied to the molecular endocrinology of TST's actions through AR will offer new avenues of enquiry into ASD. Since the high male preponderance in autism is important yet understudied, we offer our theory, which is based on detailed neurobehavioral research with animals, to stimulate basic and clinical research in animals and humans and hopefully help develop novel more effective medical treatments for autism. En ligne : http://dx.doi.org/10.1002/aur.191 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

Phonology and vocal behavior in toddlers with autism spectrum disorders / Elizabeth SCHOEN in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.177-188 Titre : Phonology and vocal behavior in toddlers with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth SCHOEN, Auteur ; Rhea PAUL, Auteur ; Katarzyna CHAWARSKA, Auteur Année de publication : 2011 Article en page(s) : p.177-188 Langues : Anglais (eng) Mots-clés : autism  phonology  autism spectrum disorders  atypical  vocalizations Index. décimale : PER Périodiques Résumé : The purpose of this study is to examine the phonological and other vocal productions of children, 18–36 months, with autism spectrum disorder (ASD) and to compare these productions to those of age-matched and language-matched controls. Speech samples were obtained from 30 toddlers with ASD, 11 age-matched toddlers and 23 language-matched toddlers during either parent–child or clinician–child play sessions. Samples were coded for a variety of speech-like and nonspeech vocalization productions. Toddlers with ASD produced speech-like vocalizations similar to those of language-matched peers, but produced significantly more atypical nonspeech vocalizations when compared to both control groups. Toddlers with ASD show speech-like sound production that is linked to their language level, in a manner similar to that seen in typical development. The main area of difference in vocal development in this population is in the production of atypical vocalizations. Findings suggest that toddlers with ASDs do not tune into the language model of their environment. Failure to attend to the ambient language environment negatively impacts the ability to acquire spoken language. En ligne : http://dx.doi.org/10.1002/aur.183 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] Phonology and vocal behavior in toddlers with autism spectrum disorders [Texte imprimé et/ou numérique] / Elizabeth SCHOEN, Auteur ; Rhea PAUL, Auteur ; Katarzyna CHAWARSKA, Auteur . - 2011 . - p.177-188. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.177-188 Mots-clés : autism  phonology  autism spectrum disorders  atypical  vocalizations Index. décimale : PER Périodiques Résumé : The purpose of this study is to examine the phonological and other vocal productions of children, 18–36 months, with autism spectrum disorder (ASD) and to compare these productions to those of age-matched and language-matched controls. Speech samples were obtained from 30 toddlers with ASD, 11 age-matched toddlers and 23 language-matched toddlers during either parent–child or clinician–child play sessions. Samples were coded for a variety of speech-like and nonspeech vocalization productions. Toddlers with ASD produced speech-like vocalizations similar to those of language-matched peers, but produced significantly more atypical nonspeech vocalizations when compared to both control groups. Toddlers with ASD show speech-like sound production that is linked to their language level, in a manner similar to that seen in typical development. The main area of difference in vocal development in this population is in the production of atypical vocalizations. Findings suggest that toddlers with ASDs do not tune into the language model of their environment. Failure to attend to the ambient language environment negatively impacts the ability to acquire spoken language. En ligne : http://dx.doi.org/10.1002/aur.183 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

Contactin 4 as an autism susceptibility locus / Catherine E. COTTRELL in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.189-199 Titre : Contactin 4 as an autism susceptibility locus Type de document : Texte imprimé et/ou numérique Auteurs : Catherine E. COTTRELL, Auteur ; Natalie BIR, Auteur ; Elizabeth A. VARGA, Auteur ; Carlos E. ALVAREZ, Auteur ; Samuel BOUYAIN, Auteur ; Randall ZERNZACH, Auteur ; Devon L. THRUSH, Auteur ; Johnna EVANS, Auteur ; Michael TRIMARCHI, Auteur ; Eric BUTTER, Auteur ; David CUNNINGHAM, Auteur ; Julie M. GASTIER-FOSTER, Auteur ; Kim L. MCBRIDE, Auteur ; Gail E. HERMAN, Auteur Année de publication : 2011 Article en page(s) : p.189-199 Langues : Anglais (eng) Mots-clés : contactin 4  autism  autism spectrum disorder  3p26 deletion  contactins  susceptibility locus Index. décimale : PER Périodiques Résumé : Structural and sequence variation have been described in several members of the contactin (CNTN) and contactin-associated protein (CNTNAP) gene families in association with neurodevelopmental disorders, including autism. Using array comparative genome hybridization (CGH), we identified a maternally inherited ∼535 kb deletion at 3p26.3 encompassing the 5′ end of the contactin 4 gene (CNTN4) in a patient with autism. Based on this finding and previous reports implicating genomic rearrangements of CNTN4 in autism spectrum disorders (ASDs) and 3p− microdeletion syndrome, we undertook sequencing of the coding regions of the gene in a local ASD cohort in comparison with a set of controls. Unique missense variants were identified in 4 of 75 unrelated individuals with ASD, as well as in 1 of 107 controls. All of the amino acid substitutions were nonsynonomous, occurred at evolutionarily conserved positions, and were, thus, felt likely to be deleterious. However, these data did not reach statistical significance, nor did the variants segregate with disease within all of the ASD families. Finally, there was no detectable difference in binding of two of the variants to the interacting protein PTPRG in vitro. Thus, additional larger studies will be necessary to determine whether CNTN4 functions as an autism susceptibility locus in combination with other genetic and/or environmental factors. En ligne : http://dx.doi.org/10.1002/aur.184 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] Contactin 4 as an autism susceptibility locus [Texte imprimé et/ou numérique] / Catherine E. COTTRELL, Auteur ; Natalie BIR, Auteur ; Elizabeth A. VARGA, Auteur ; Carlos E. ALVAREZ, Auteur ; Samuel BOUYAIN, Auteur ; Randall ZERNZACH, Auteur ; Devon L. THRUSH, Auteur ; Johnna EVANS, Auteur ; Michael TRIMARCHI, Auteur ; Eric BUTTER, Auteur ; David CUNNINGHAM, Auteur ; Julie M. GASTIER-FOSTER, Auteur ; Kim L. MCBRIDE, Auteur ; Gail E. HERMAN, Auteur . - 2011 . - p.189-199. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.189-199 Mots-clés : contactin 4  autism  autism spectrum disorder  3p26 deletion  contactins  susceptibility locus Index. décimale : PER Périodiques Résumé : Structural and sequence variation have been described in several members of the contactin (CNTN) and contactin-associated protein (CNTNAP) gene families in association with neurodevelopmental disorders, including autism. Using array comparative genome hybridization (CGH), we identified a maternally inherited ∼535 kb deletion at 3p26.3 encompassing the 5′ end of the contactin 4 gene (CNTN4) in a patient with autism. Based on this finding and previous reports implicating genomic rearrangements of CNTN4 in autism spectrum disorders (ASDs) and 3p− microdeletion syndrome, we undertook sequencing of the coding regions of the gene in a local ASD cohort in comparison with a set of controls. Unique missense variants were identified in 4 of 75 unrelated individuals with ASD, as well as in 1 of 107 controls. All of the amino acid substitutions were nonsynonomous, occurred at evolutionarily conserved positions, and were, thus, felt likely to be deleterious. However, these data did not reach statistical significance, nor did the variants segregate with disease within all of the ASD families. Finally, there was no detectable difference in binding of two of the variants to the interacting protein PTPRG in vitro. Thus, additional larger studies will be necessary to determine whether CNTN4 functions as an autism susceptibility locus in combination with other genetic and/or environmental factors. En ligne : http://dx.doi.org/10.1002/aur.184 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism / Adrian L. OBLAK in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.200-211 Titre : Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism Type de document : Texte imprimé et/ou numérique Auteurs : Adrian L. OBLAK, Auteur ; Douglas L. ROSENE, Auteur ; Thomas L. KEMPER, Auteur ; Margaret L. BAUMAN, Auteur ; Gene J. BLATT, Auteur Année de publication : 2011 Article en page(s) : p.200-211 Langues : Anglais (eng) Mots-clés : neuropathology  gamma-aminobutyric acid  neurochemistry ;neuroanatomy Index. décimale : PER Périodiques Résumé : Autism is a developmental disorder with prenatal origins, currently estimated to affect 1 in 91 children in the United States. Social-emotional deficits are a hallmark of autism and early neuropathology studies have indicated involvement of the limbic system. Imaging studies demonstrate abnormal activation of the posterior cingulate cortex (PCC), a component of the limbic system. Abnormal activation has also been noted in the fusiform gyrus (FFG), a region important for facial recognition and a key element in social interaction. A potential imbalance between excitatory and inhibitory interneurons in the cortex may contribute to altered information processing in autism. Furthermore, reduced numbers of GABA receptors have previously been reported in the autistic brain. Thionin-stained sections were used to qualitatively assess cytoarchitectonic patterning and quantitatively determine the density of neurons and immunohistochemistry was used to determine the densities of a subset of GABAergic interneurons utilizing parvalbumin-and calbindin-immunoreactivity. In autism, the PCC displayed altered cytoarchitecture with irregularly distributed neurons, poorly demarcated layers IV and V, and increased presence of white matter neurons. In contrast, no neuropathology was observed in the FFG. There was no significant difference in the density of thionin, parvalbumin, or calbindin interneurons in either region and there was a trend towards a reduced density of calbindin neurons in the PCC. This study highlights the presence of abnormal findings in the PCC, which appear to be developmental in nature and could affect the local processing of social–emotional behaviors as well as functioning of interrelated areas. En ligne : http://dx.doi.org/10.1002/aur.188 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism [Texte imprimé et/ou numérique] / Adrian L. OBLAK, Auteur ; Douglas L. ROSENE, Auteur ; Thomas L. KEMPER, Auteur ; Margaret L. BAUMAN, Auteur ; Gene J. BLATT, Auteur . - 2011 . - p.200-211. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.200-211 Mots-clés : neuropathology  gamma-aminobutyric acid  neurochemistry ;neuroanatomy Index. décimale : PER Périodiques Résumé : Autism is a developmental disorder with prenatal origins, currently estimated to affect 1 in 91 children in the United States. Social-emotional deficits are a hallmark of autism and early neuropathology studies have indicated involvement of the limbic system. Imaging studies demonstrate abnormal activation of the posterior cingulate cortex (PCC), a component of the limbic system. Abnormal activation has also been noted in the fusiform gyrus (FFG), a region important for facial recognition and a key element in social interaction. A potential imbalance between excitatory and inhibitory interneurons in the cortex may contribute to altered information processing in autism. Furthermore, reduced numbers of GABA receptors have previously been reported in the autistic brain. Thionin-stained sections were used to qualitatively assess cytoarchitectonic patterning and quantitatively determine the density of neurons and immunohistochemistry was used to determine the densities of a subset of GABAergic interneurons utilizing parvalbumin-and calbindin-immunoreactivity. In autism, the PCC displayed altered cytoarchitecture with irregularly distributed neurons, poorly demarcated layers IV and V, and increased presence of white matter neurons. In contrast, no neuropathology was observed in the FFG. There was no significant difference in the density of thionin, parvalbumin, or calbindin interneurons in either region and there was a trend towards a reduced density of calbindin neurons in the PCC. This study highlights the presence of abnormal findings in the PCC, which appear to be developmental in nature and could affect the local processing of social–emotional behaviors as well as functioning of interrelated areas. En ligne : http://dx.doi.org/10.1002/aur.188 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

Basal ganglia morphometry and repetitive behavior in young children with autism spectrum disorder / Annette ESTES in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.212-220 Titre : Basal ganglia morphometry and repetitive behavior in young children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Annette ESTES, Auteur ; Dennis W.W. SHAW, Auteur ; Bobbi F. SPARKS, Auteur ; Seth D. FRIEDMAN, Auteur ; Jay N. GIEDD, Auteur ; Geraldine DAWSON, Auteur ; Matthew BRYAN, Auteur ; Stephen R. DAGER, Auteur Année de publication : 2011 Article en page(s) : p.212-220 Langues : Anglais (eng) Mots-clés : neuroimaging  preschoolers  clinical psychology  repetitive behavior  autism spectrum disorders Index. décimale : PER Périodiques Résumé : We investigated repetitive and stereotyped behavior (RSB) and its relationship to morphometric measures of the basal ganglia and thalami in 3- to 4-year-old children with autism spectrum disorder (ASD; n = 77) and developmental delay without autism (DD; n = 34). Children were assessed through clinical evaluation and parent report using RSB-specific scales extracted from the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview, and the Aberrant Behavior Checklist. A subset of children with ASD (n = 45), DD (n = 14), and a group of children with typical development (TD; n = 25) were also assessed by magnetic resonance imaging. Children with ASD demonstrated elevated RSB across all measures compared to children with DD. Enlargement of the left and right striatum, more specifically the left and right putamen, and left caudate, was observed in the ASD compared to the TD group. However, nuclei were not significantly enlarged after controlling for cerebral volume. The DD group, in comparison to the ASD group, demonstrated smaller thalami and basal ganglia regions even when scaled for cerebral volume, with the exception of the left striatum, left putamen, and right putamen. Elevated RSB, as measured by the ADOS, was associated with decreased volumes in several brain regions: left thalamus, right globus pallidus, left and right putamen, right striatum and a trend for left globus pallidus and left striatum within the ASD group. These results confirm earlier reports that RSB is common early in the clinical course of ASD and, furthermore, demonstrate that such behaviors may be associated with decreased volumes of the basal ganglia and thalamus. En ligne : http://dx.doi.org/10.1002/aur.193 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] Basal ganglia morphometry and repetitive behavior in young children with autism spectrum disorder [Texte imprimé et/ou numérique] / Annette ESTES, Auteur ; Dennis W.W. SHAW, Auteur ; Bobbi F. SPARKS, Auteur ; Seth D. FRIEDMAN, Auteur ; Jay N. GIEDD, Auteur ; Geraldine DAWSON, Auteur ; Matthew BRYAN, Auteur ; Stephen R. DAGER, Auteur . - 2011 . - p.212-220. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.212-220 Mots-clés : neuroimaging  preschoolers  clinical psychology  repetitive behavior  autism spectrum disorders Index. décimale : PER Périodiques Résumé : We investigated repetitive and stereotyped behavior (RSB) and its relationship to morphometric measures of the basal ganglia and thalami in 3- to 4-year-old children with autism spectrum disorder (ASD; n = 77) and developmental delay without autism (DD; n = 34). Children were assessed through clinical evaluation and parent report using RSB-specific scales extracted from the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview, and the Aberrant Behavior Checklist. A subset of children with ASD (n = 45), DD (n = 14), and a group of children with typical development (TD; n = 25) were also assessed by magnetic resonance imaging. Children with ASD demonstrated elevated RSB across all measures compared to children with DD. Enlargement of the left and right striatum, more specifically the left and right putamen, and left caudate, was observed in the ASD compared to the TD group. However, nuclei were not significantly enlarged after controlling for cerebral volume. The DD group, in comparison to the ASD group, demonstrated smaller thalami and basal ganglia regions even when scaled for cerebral volume, with the exception of the left striatum, left putamen, and right putamen. Elevated RSB, as measured by the ADOS, was associated with decreased volumes in several brain regions: left thalamus, right globus pallidus, left and right putamen, right striatum and a trend for left globus pallidus and left striatum within the ASD group. These results confirm earlier reports that RSB is common early in the clinical course of ASD and, furthermore, demonstrate that such behaviors may be associated with decreased volumes of the basal ganglia and thalamus. En ligne : http://dx.doi.org/10.1002/aur.193 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis / Anthony J. GRISWOLD in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.221-227 Titre : A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis Type de document : Texte imprimé et/ou numérique Auteurs : Anthony J. GRISWOLD, Auteur ; Deqiong MA, Auteur ; Stephanie J. SACHAROW, Auteur ; Joycelyn L. ROBINSON, Auteur ; James M. JAWORSKI, Auteur ; Harry H. WRIGHT, Auteur ; Ruth K. ABRAMSON, Auteur ; Helle LYBAEK, Auteur ; Nina OYEN, Auteur ; Michael L. CUCCARO, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur Année de publication : 2011 Article en page(s) : p.221-227 Langues : Anglais (eng) Mots-clés : genetics  copy number variation  molecular genetics Index. décimale : PER Périodiques Résumé : Autism is a neuro-developmental disorder characterized by deficits in social interaction and communication as well as restricted interests or repetitive behaviors. Cytogenetic studies have implicated large chromosomal aberrations in the etiology of approximately 5–7% of autism patients, and the recent advent of array-based techniques allows the exploration of submicroscopic copy number variations (CNVs). We genotyped a 14-year-old boy with autism, spherocytosis and other physical dysmorphia, his parents, and two non-autistic siblings with the Illumina Human 1M Beadchip as part of a study of the molecular genetics of autism and determined copy number variants using the PennCNV algorithm. We identified and validated a de novo 1.5 Mb microdeletion of 14q23.2-23.3 in our autistic patient. This region contains 15 genes, including spectrin beta (SPTB), encoding a cytoskeletal protein previously associated with spherocytosis, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a folate metabolizing enzyme previously associated with bipoloar disorder and schizophrenia, pleckstrin homology domain-containing family G member 3 (PLEKHG3), a guanide nucleotide exchange enriched in the brain, and churchill domain containing protein 1 (CHURC1), homologs of which regulate neuronal development in model organisms. While a similar deletion has previously been reported in a family with spherocytosis, severe learning disabilities, and mild mental retardation, this is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk. En ligne : http://dx.doi.org/10.1002/aur.186 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis [Texte imprimé et/ou numérique] / Anthony J. GRISWOLD, Auteur ; Deqiong MA, Auteur ; Stephanie J. SACHAROW, Auteur ; Joycelyn L. ROBINSON, Auteur ; James M. JAWORSKI, Auteur ; Harry H. WRIGHT, Auteur ; Ruth K. ABRAMSON, Auteur ; Helle LYBAEK, Auteur ; Nina OYEN, Auteur ; Michael L. CUCCARO, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur . - 2011 . - p.221-227. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.221-227 Mots-clés : genetics  copy number variation  molecular genetics Index. décimale : PER Périodiques Résumé : Autism is a neuro-developmental disorder characterized by deficits in social interaction and communication as well as restricted interests or repetitive behaviors. Cytogenetic studies have implicated large chromosomal aberrations in the etiology of approximately 5–7% of autism patients, and the recent advent of array-based techniques allows the exploration of submicroscopic copy number variations (CNVs). We genotyped a 14-year-old boy with autism, spherocytosis and other physical dysmorphia, his parents, and two non-autistic siblings with the Illumina Human 1M Beadchip as part of a study of the molecular genetics of autism and determined copy number variants using the PennCNV algorithm. We identified and validated a de novo 1.5 Mb microdeletion of 14q23.2-23.3 in our autistic patient. This region contains 15 genes, including spectrin beta (SPTB), encoding a cytoskeletal protein previously associated with spherocytosis, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a folate metabolizing enzyme previously associated with bipoloar disorder and schizophrenia, pleckstrin homology domain-containing family G member 3 (PLEKHG3), a guanide nucleotide exchange enriched in the brain, and churchill domain containing protein 1 (CHURC1), homologs of which regulate neuronal development in model organisms. While a similar deletion has previously been reported in a family with spherocytosis, severe learning disabilities, and mild mental retardation, this is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk. En ligne : http://dx.doi.org/10.1002/aur.186 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

Fine mapping of Xq11.1-q21.33 and mutation screening of RPS6KA6, ZNF711, ACSL4, DLG3, and IL1RAPL2 for autism spectrum disorders (ASD) / Katri KANTOJARVI in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.228-233 Titre : Fine mapping of Xq11.1-q21.33 and mutation screening of RPS6KA6, ZNF711, ACSL4, DLG3, and IL1RAPL2 for autism spectrum disorders (ASD) Type de document : Texte imprimé et/ou numérique Auteurs : Katri KANTOJARVI, Auteur ; Ilona KOTALA, Auteur ; Karola REHNSTROM, Auteur ; Tero YLISAUKKO-OJA, Auteur ; Raija VANHALA, Auteur ; Taina NIEMINEN-VON WENDT, Auteur ; Lennart VON WENDT, Auteur ; Irma JARVELA, Auteur Année de publication : 2011 Article en page(s) : p.228-233 Langues : Anglais (eng) Mots-clés : ACSL4  autism spectrum disorders  DLG3  gene  IL1RAPL2  linkage  RPS6KA6  single nucleotide polymorphism  ZNF711  XLMR Index. décimale : PER Périodiques Résumé : About 80% of cases with autism express intellectual disability. Both in autism and in mental retardation without autism the majority of the cases are males, suggesting a X-chromosomal effect. In fact, some molecular evidence has been obtained for a common genetic background for autism spectrum disorders (ASD) and X-linked mental retardation (XLMR). In several genome-wide scans (GWS), evidence for linkage at X-chromosome has been reported including the GWS of Finnish ASD families with the highest multipoint lod score (MLS) of 2.75 obtained close to DXS7132 at Xq11.1. To further dissect the relationship between autism and genes implicated in XLMR, we have fine-mapped Xq11.1-q21.33 and analyzed five candidate genes in the region. We refined the region using 26 microsatellite markers and linkage analysis in 99 Finnish families with ASD. The most significant evidence for linkage was observed at DXS1225 on Xq21.1 with a nonparametric multipoint NPLall value of 3.43 (P = 0.0004). We sequenced the coding regions and splice sites of RPS6KA6 and ZNF711 residing at the peak region in 42 male patients from families contributing to the linkage. We also analyzed ACSL4 and DLG3, which have previously been known to cause XLMR and IL1RAPL2, a homologous gene for IL1RAPL1 that is mutated in autism and XLMR. A total of six novel and 11 known single nucleotide polymorphisms were identified. Further studies are warranted to analyze the candidate genes at Xq11.1-q21.33. En ligne : http://dx.doi.org/10.1002/aur.187 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] Fine mapping of Xq11.1-q21.33 and mutation screening of RPS6KA6, ZNF711, ACSL4, DLG3, and IL1RAPL2 for autism spectrum disorders (ASD) [Texte imprimé et/ou numérique] / Katri KANTOJARVI, Auteur ; Ilona KOTALA, Auteur ; Karola REHNSTROM, Auteur ; Tero YLISAUKKO-OJA, Auteur ; Raija VANHALA, Auteur ; Taina NIEMINEN-VON WENDT, Auteur ; Lennart VON WENDT, Auteur ; Irma JARVELA, Auteur . - 2011 . - p.228-233. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.228-233 Mots-clés : ACSL4  autism spectrum disorders  DLG3  gene  IL1RAPL2  linkage  RPS6KA6  single nucleotide polymorphism  ZNF711  XLMR Index. décimale : PER Périodiques Résumé : About 80% of cases with autism express intellectual disability. Both in autism and in mental retardation without autism the majority of the cases are males, suggesting a X-chromosomal effect. In fact, some molecular evidence has been obtained for a common genetic background for autism spectrum disorders (ASD) and X-linked mental retardation (XLMR). In several genome-wide scans (GWS), evidence for linkage at X-chromosome has been reported including the GWS of Finnish ASD families with the highest multipoint lod score (MLS) of 2.75 obtained close to DXS7132 at Xq11.1. To further dissect the relationship between autism and genes implicated in XLMR, we have fine-mapped Xq11.1-q21.33 and analyzed five candidate genes in the region. We refined the region using 26 microsatellite markers and linkage analysis in 99 Finnish families with ASD. The most significant evidence for linkage was observed at DXS1225 on Xq21.1 with a nonparametric multipoint NPLall value of 3.43 (P = 0.0004). We sequenced the coding regions and splice sites of RPS6KA6 and ZNF711 residing at the peak region in 42 male patients from families contributing to the linkage. We also analyzed ACSL4 and DLG3, which have previously been known to cause XLMR and IL1RAPL2, a homologous gene for IL1RAPL1 that is mutated in autism and XLMR. A total of six novel and 11 known single nucleotide polymorphisms were identified. Further studies are warranted to analyze the candidate genes at Xq11.1-q21.33. En ligne : http://dx.doi.org/10.1002/aur.187 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

Lay abstracts in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.234-236 Titre : Lay abstracts Type de document : Texte imprimé et/ou numérique Année de publication : 2011 Article en page(s) : p.234-236 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.203 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] Lay abstracts [Texte imprimé et/ou numérique] . - 2011 . - p.234-236. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.234-236 Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.203 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

International Society for Autism Research News in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.236 Titre : International Society for Autism Research News Type de document : Texte imprimé et/ou numérique Année de publication : 2011 Article en page(s) : p.236 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.206 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] International Society for Autism Research News [Texte imprimé et/ou numérique] . - 2011 . - p.236. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.236 Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.206 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127