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Facial phenotypes in subgroups of prepubertal boys with autism spectrum disorders are correlated with clinical phenotypes / Kristina ALDRIDGE in Molecular Autism, (October 2011)  

Public ISBD [article]  inMolecular Autism > (October 2011) . - 12 p. Titre : Facial phenotypes in subgroups of prepubertal boys with autism spectrum disorders are correlated with clinical phenotypes Type de document : Texte imprimé et/ou numérique Auteurs : Kristina ALDRIDGE, Auteur ; Ian GEORGE, Auteur ; Kimberly COLE, Auteur ; Jordan AUSTIN, Auteur ; T. Nicole TAKAHASHI, Auteur ; Ye DUAN, Auteur ; Judith H. MILES, Auteur Année de publication : 2011 Article en page(s) : 12 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:The brain develops in concert and in coordination with the developing facial tissues, with each influencing the development of the other and sharing genetic signaling pathways. Autism spectrum disorders (ASDs) result from alterations in the embryological brain, suggesting that the development of the faces of children with ASD may result in subtle facial differences compared to typically developing children. In this study, we tested two hypotheses. First, we asked whether children with ASD display a subtle but distinct facial phenotype compared to typically developing children. Second, we sought to determine whether there are subgroups of facial phenotypes within the population of children with ASD that denote biologically discrete subgroups.METHODS:The 3dMD cranial System was used to acquire three-dimensional stereophotogrammetric images for our study sample of 8- to 12-year-old boys diagnosed with essential ASD (n = 65) and typically developing boys (n = 41) following approved Institutional Review Board protocols. Three-dimensional coordinates were recorded for 17 facial anthropometric landmarks using the 3dMD Patient software. Statistical comparisons of facial phenotypes were completed using Euclidean Distance Matrix Analysis and Principal Coordinates Analysis. Data representing clinical and behavioral traits were statistically compared among groups by using chi2 tests, Fisher's exact tests, Kolmogorov-Smirnov tests and Student's t-tests where appropriate.RESULTS:First, we found that there are significant differences in facial morphology in boys with ASD compared to typically developing boys. Second, we also found two subgroups of boys with ASD with facial morphology that differed from the majority of the boys with ASD and the typically developing boys. Furthermore, membership in each of these distinct subgroups was correlated with particular clinical and behavioral traits.CONCLUSIONS:Boys with ASD display a facial phenotype distinct from that of typically developing boys, which may reflect alterations in the prenatal development of the brain. Subgroups of boys with ASD defined by distinct facial morphologies correlated with clinical and behavioral traits, suggesting potentially different etiologies and genetic differences compared to the larger group of boys with ASD. Further investigations into genes involved in neurodevelopment and craniofacial development of these subgroups will help to elucidate the causes and significance of these subtle facial differences. En ligne : http://dx.doi.org/10.1186/2040-2392-2-15 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149 [article] Facial phenotypes in subgroups of prepubertal boys with autism spectrum disorders are correlated with clinical phenotypes [Texte imprimé et/ou numérique] / Kristina ALDRIDGE, Auteur ; Ian GEORGE, Auteur ; Kimberly COLE, Auteur ; Jordan AUSTIN, Auteur ; T. Nicole TAKAHASHI, Auteur ; Ye DUAN, Auteur ; Judith H. MILES, Auteur . - 2011 . - 12 p. Langues : Anglais (eng) in Molecular Autism > (October 2011) . - 12 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:The brain develops in concert and in coordination with the developing facial tissues, with each influencing the development of the other and sharing genetic signaling pathways. Autism spectrum disorders (ASDs) result from alterations in the embryological brain, suggesting that the development of the faces of children with ASD may result in subtle facial differences compared to typically developing children. In this study, we tested two hypotheses. First, we asked whether children with ASD display a subtle but distinct facial phenotype compared to typically developing children. Second, we sought to determine whether there are subgroups of facial phenotypes within the population of children with ASD that denote biologically discrete subgroups.METHODS:The 3dMD cranial System was used to acquire three-dimensional stereophotogrammetric images for our study sample of 8- to 12-year-old boys diagnosed with essential ASD (n = 65) and typically developing boys (n = 41) following approved Institutional Review Board protocols. Three-dimensional coordinates were recorded for 17 facial anthropometric landmarks using the 3dMD Patient software. Statistical comparisons of facial phenotypes were completed using Euclidean Distance Matrix Analysis and Principal Coordinates Analysis. Data representing clinical and behavioral traits were statistically compared among groups by using chi2 tests, Fisher's exact tests, Kolmogorov-Smirnov tests and Student's t-tests where appropriate.RESULTS:First, we found that there are significant differences in facial morphology in boys with ASD compared to typically developing boys. Second, we also found two subgroups of boys with ASD with facial morphology that differed from the majority of the boys with ASD and the typically developing boys. Furthermore, membership in each of these distinct subgroups was correlated with particular clinical and behavioral traits.CONCLUSIONS:Boys with ASD display a facial phenotype distinct from that of typically developing boys, which may reflect alterations in the prenatal development of the brain. Subgroups of boys with ASD defined by distinct facial morphologies correlated with clinical and behavioral traits, suggesting potentially different etiologies and genetic differences compared to the larger group of boys with ASD. Further investigations into genes involved in neurodevelopment and craniofacial development of these subgroups will help to elucidate the causes and significance of these subtle facial differences. En ligne : http://dx.doi.org/10.1186/2040-2392-2-15 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149

Investigation of the serum levels of anterior pituitary hormones in male children with autism / Keiko IWATA in Molecular Autism, (October 2011)  

Public ISBD [article]  inMolecular Autism > (October 2011) . - 6 p. Titre : Investigation of the serum levels of anterior pituitary hormones in male children with autism Type de document : Texte imprimé et/ou numérique Auteurs : Keiko IWATA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Chie SHIMMURA, Auteur ; Shiro SUDA, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Katsuaki SUZUKI, Auteur ; Yasuhide IWATA, Auteur ; Kazuhiko NAKAMURA, Auteur ; Masatsugu TSUJII, Auteur ; Toshiro SUGIYAMA, Auteur ; Kohji SATO, Auteur ; Norio MORI, Auteur Année de publication : 2011 Article en page(s) : 6 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:The neurobiological basis of autism remains poorly understood. The diagnosis of autism is based solely on behavioural characteristics because there are currently no reliable biological markers. To test whether the anterior pituitary hormones and cortisol could be useful as biological markers for autism, we assessed the basal serum levels of these hormones in subjects with autism and normal controls.FINDINGS:Using a suspension array system, we determined the serum levels of six anterior pituitary hormones, including adrenocorticotropic hormone and growth hormone, in 32 drug-naive subjects (aged 6 to 18 years, all boys) with autism, and 34 healthy controls matched for age and gender. We also determined cortisol levels in these subjects by enzyme-linked immunosorbent assay. Serum levels of adrenocorticotropic hormone, growth hormone and cortisol were significantly higher in subjects with autism than in controls. In addition, there was a significantly positive correlation between cortisol and adrenocorticotropic hormone levels in autism.CONCLUSION:Our results suggest that increased basal serum levels of adrenocorticotropic hormone accompanied by increased cortisol and growth hormone may be useful biological markers for autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149 [article] Investigation of the serum levels of anterior pituitary hormones in male children with autism [Texte imprimé et/ou numérique] / Keiko IWATA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Chie SHIMMURA, Auteur ; Shiro SUDA, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Katsuaki SUZUKI, Auteur ; Yasuhide IWATA, Auteur ; Kazuhiko NAKAMURA, Auteur ; Masatsugu TSUJII, Auteur ; Toshiro SUGIYAMA, Auteur ; Kohji SATO, Auteur ; Norio MORI, Auteur . - 2011 . - 6 p. Langues : Anglais (eng) in Molecular Autism > (October 2011) . - 6 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:The neurobiological basis of autism remains poorly understood. The diagnosis of autism is based solely on behavioural characteristics because there are currently no reliable biological markers. To test whether the anterior pituitary hormones and cortisol could be useful as biological markers for autism, we assessed the basal serum levels of these hormones in subjects with autism and normal controls.FINDINGS:Using a suspension array system, we determined the serum levels of six anterior pituitary hormones, including adrenocorticotropic hormone and growth hormone, in 32 drug-naive subjects (aged 6 to 18 years, all boys) with autism, and 34 healthy controls matched for age and gender. We also determined cortisol levels in these subjects by enzyme-linked immunosorbent assay. Serum levels of adrenocorticotropic hormone, growth hormone and cortisol were significantly higher in subjects with autism than in controls. In addition, there was a significantly positive correlation between cortisol and adrenocorticotropic hormone levels in autism.CONCLUSION:Our results suggest that increased basal serum levels of adrenocorticotropic hormone accompanied by increased cortisol and growth hormone may be useful biological markers for autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149

Autism risk assessment in siblings of affected children using sex-specific genetic scores / Jerome CARAYOL in Molecular Autism, (October 2011)  

Public ISBD [article]  inMolecular Autism > (October 2011) . - 8 p. Titre : Autism risk assessment in siblings of affected children using sex-specific genetic scores Type de document : Texte imprimé et/ou numérique Auteurs : Jerome CARAYOL, Auteur ; Gerard SCHELLENBERG, Auteur ; Beth DOMBROSKI, Auteur ; Emmanuelle GENIN, Auteur ; Francis ROUSSEAU, Auteur ; Geraldine DAWSON, Auteur Année de publication : 2011 Article en page(s) : 8 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:The inheritance pattern in most cases of autism is complex. The risk of autism is increased in siblings of children with autism and previous studies have indicated that the level of risk can be further identified by the accumulation of multiple susceptibility single nucleotide polymorphisms (SNPs) allowing for the identification of a higher-risk subgroup among siblings. As a result of the sex difference in the prevalence of autism, we explored the potential for identifying sex-specific autism susceptibility SNPs in siblings of children with autism and the ability to develop a sex-specific risk assessment genetic scoring system.METHODS:SNPs were chosen from genes known to be associated with autism. These markers were evaluated using an exploratory sample of 480 families from the Autism Genetic Resource Exchange (AGRE) repository. A reproducibility index (RI) was proposed and calculated in all children with autism and in males and females separately. Differing genetic scoring models were then constructed to develop a sex-specific genetic score model designed to identify individuals with a higher risk of autism. The ability of the genetic scores to identify high-risk children was then evaluated and replicated in an independent sample of 351 affected and 90 unaffected siblings from families with at least 1 child with autism.RESULTS:We identified three risk SNPs that had a high RI in males, two SNPs with a high RI in females, and three SNPs with a high RI in both sexes. Using these results, genetic scoring models for males and females were developed which demonstrated a significant association with autism (P = 2.2 x 10-6 and 1.9 x 10-5, respectively).CONCLUSIONS:Our results demonstrate that individual susceptibility associated SNPs for autism may have important differential sex effects. We also show that a sex-specific risk score based on the presence of multiple susceptibility associated SNPs allow for the identification of subgroups of siblings of children with autism who have a significantly higher risk of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149 [article] Autism risk assessment in siblings of affected children using sex-specific genetic scores [Texte imprimé et/ou numérique] / Jerome CARAYOL, Auteur ; Gerard SCHELLENBERG, Auteur ; Beth DOMBROSKI, Auteur ; Emmanuelle GENIN, Auteur ; Francis ROUSSEAU, Auteur ; Geraldine DAWSON, Auteur . - 2011 . - 8 p. Langues : Anglais (eng) in Molecular Autism > (October 2011) . - 8 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:The inheritance pattern in most cases of autism is complex. The risk of autism is increased in siblings of children with autism and previous studies have indicated that the level of risk can be further identified by the accumulation of multiple susceptibility single nucleotide polymorphisms (SNPs) allowing for the identification of a higher-risk subgroup among siblings. As a result of the sex difference in the prevalence of autism, we explored the potential for identifying sex-specific autism susceptibility SNPs in siblings of children with autism and the ability to develop a sex-specific risk assessment genetic scoring system.METHODS:SNPs were chosen from genes known to be associated with autism. These markers were evaluated using an exploratory sample of 480 families from the Autism Genetic Resource Exchange (AGRE) repository. A reproducibility index (RI) was proposed and calculated in all children with autism and in males and females separately. Differing genetic scoring models were then constructed to develop a sex-specific genetic score model designed to identify individuals with a higher risk of autism. The ability of the genetic scores to identify high-risk children was then evaluated and replicated in an independent sample of 351 affected and 90 unaffected siblings from families with at least 1 child with autism.RESULTS:We identified three risk SNPs that had a high RI in males, two SNPs with a high RI in females, and three SNPs with a high RI in both sexes. Using these results, genetic scoring models for males and females were developed which demonstrated a significant association with autism (P = 2.2 x 10-6 and 1.9 x 10-5, respectively).CONCLUSIONS:Our results demonstrate that individual susceptibility associated SNPs for autism may have important differential sex effects. We also show that a sex-specific risk score based on the presence of multiple susceptibility associated SNPs allow for the identification of subgroups of siblings of children with autism who have a significantly higher risk of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149