Enhancing multi-site autism research through the development of a collaborative data platform / Jeffrey D. ROTH ; Kashia A. ROSENAU ; Patrick S. DWYER ; Alice A. KUO ; Julian A. MARTINEZ-AGOSTO in Autism Research, 17-7 (July 2024)  

Public ISBD [article]  inAutism Research > 17-7 (July 2024) . - p.1322-1327 Titre : Enhancing multi-site autism research through the development of a collaborative data platform Type de document : Texte imprimé et/ou numérique Auteurs : Jeffrey D. ROTH, Auteur ; Kashia A. ROSENAU, Auteur ; Patrick S. DWYER, Auteur ; Alice A. KUO, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur Article en page(s) : p.1322-1327 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Data repositories, particularly those storing data on vulnerable populations, increasingly need to carefully consider not only what data is being collected, but how it will be used. As such, the Autism Intervention Research Network on Physical Health (AIR-P) has created the Infrastructure for Collaborative Research (ICR) to establish standards on data collection practices in Autism repositories. The ICR will strive to encourage inter-site collaboration, amplify autistic voices, and widen accessibility to data. The ICR is staged as a three-tiered framework consisting of (1) a request for proposals system, (2) a REDCap-based data repository, and (3) public data dashboards to display aggregate de-identified data. Coupled with a review process including autistic and non-autistic researchers, this framework aims to propel the implementation of equitable autism research, enhance standardization within and between studies, and boost transparency and dissemination of findings. In addition, the inclusion of a contact registry that study participants can opt into creates the base for a robust participant pool. As such, researchers can leverage the platform to identify, reach, and distribute electronic materials to a greater proportion of potential participants who likely fall within their eligibility criteria. By incorporating practices that promote effective communication between researchers and participants, the ICR can facilitate research that is both considerate of and a benefit to autistic people. En ligne : https://dx.doi.org/https://doi.org/10.1002/aur.3167 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=533 [article] Enhancing multi-site autism research through the development of a collaborative data platform [Texte imprimé et/ou numérique] / Jeffrey D. ROTH, Auteur ; Kashia A. ROSENAU, Auteur ; Patrick S. DWYER, Auteur ; Alice A. KUO, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur . - p.1322-1327. Langues : Anglais (eng) in Autism Research > 17-7 (July 2024) . - p.1322-1327 Index. décimale : PER Périodiques Résumé : Abstract Data repositories, particularly those storing data on vulnerable populations, increasingly need to carefully consider not only what data is being collected, but how it will be used. As such, the Autism Intervention Research Network on Physical Health (AIR-P) has created the Infrastructure for Collaborative Research (ICR) to establish standards on data collection practices in Autism repositories. The ICR will strive to encourage inter-site collaboration, amplify autistic voices, and widen accessibility to data. The ICR is staged as a three-tiered framework consisting of (1) a request for proposals system, (2) a REDCap-based data repository, and (3) public data dashboards to display aggregate de-identified data. Coupled with a review process including autistic and non-autistic researchers, this framework aims to propel the implementation of equitable autism research, enhance standardization within and between studies, and boost transparency and dissemination of findings. In addition, the inclusion of a contact registry that study participants can opt into creates the base for a robust participant pool. As such, researchers can leverage the platform to identify, reach, and distribute electronic materials to a greater proportion of potential participants who likely fall within their eligibility criteria. By incorporating practices that promote effective communication between researchers and participants, the ICR can facilitate research that is both considerate of and a benefit to autistic people. En ligne : https://dx.doi.org/https://doi.org/10.1002/aur.3167 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=533

Macrocephaly as a Clinical Indicator of Genetic Subtypes in Autism / Steven KLEIN in Autism Research, 6-1 (February 2013)  

Public ISBD [article]  inAutism Research > 6-1 (February 2013) . - p.51-56 Titre : Macrocephaly as a Clinical Indicator of Genetic Subtypes in Autism Type de document : Texte imprimé et/ou numérique Auteurs : Steven KLEIN, Auteur ; Pantea SHARIFI-HANNAUER, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur Année de publication : 2013 Article en page(s) : p.51-56 Langues : Anglais (eng) Mots-clés : autism  macrocephaly  PTEN  overgrowth  hypotonia Index. décimale : PER Périodiques Résumé : An association between autism and macrocephaly has been previously described. A subset of cases with extreme macrocephaly (3 standard deviation [SD], 99.7th percentile) have been correlated to mutations in the gene phosphatase and tensin homolog (PTEN). However, the phenotypic and genetic characterization of the remaining cases remains unclear. We report the phenotypic classification and genetic testing evaluation of a cohort of 33 patients with autism and macrocephaly. Within our cohort, we confirm the association of PTEN mutations and extreme macrocephaly (3 SD, 99.7th percentile) and identify mutations in 22% of cases, including three novel PTEN mutations. In addition, we define three phenotypic subgroups: (a) those cases associated with somatic overgrowth, (b) those with disproportionate macrocephaly, and (c) those with relative macrocephaly. We have devised a novel way to segregate patients into these subgroups that will aide in the stratification of autism macrocephaly cases. Within these subgroups, we further expand the genetic etiologies for autism cases with macrocephaly by describing two novel suspected pathogenic copy number variants located at 6q23.2 and 10q24.32. These findings demonstrate the phenotypic heterogeneity of autism cases associated with macrocephaly and their genetic etiologies. The clinical yield from PTEN mutation analysis is 22% and 9% from chromosomal microarray (CMA) testing within this cohort. The identification of three distinct phenotypic subgroups within macrocephaly autism patients may allow for the identification of their respective distinct genetic etiologies that to date have remained elusive. En ligne : http://dx.doi.org/10.1002/aur.1266 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=192 [article] Macrocephaly as a Clinical Indicator of Genetic Subtypes in Autism [Texte imprimé et/ou numérique] / Steven KLEIN, Auteur ; Pantea SHARIFI-HANNAUER, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur . - 2013 . - p.51-56. Langues : Anglais (eng) in Autism Research > 6-1 (February 2013) . - p.51-56 Mots-clés : autism  macrocephaly  PTEN  overgrowth  hypotonia Index. décimale : PER Périodiques Résumé : An association between autism and macrocephaly has been previously described. A subset of cases with extreme macrocephaly (3 standard deviation [SD], 99.7th percentile) have been correlated to mutations in the gene phosphatase and tensin homolog (PTEN). However, the phenotypic and genetic characterization of the remaining cases remains unclear. We report the phenotypic classification and genetic testing evaluation of a cohort of 33 patients with autism and macrocephaly. Within our cohort, we confirm the association of PTEN mutations and extreme macrocephaly (3 SD, 99.7th percentile) and identify mutations in 22% of cases, including three novel PTEN mutations. In addition, we define three phenotypic subgroups: (a) those cases associated with somatic overgrowth, (b) those with disproportionate macrocephaly, and (c) those with relative macrocephaly. We have devised a novel way to segregate patients into these subgroups that will aide in the stratification of autism macrocephaly cases. Within these subgroups, we further expand the genetic etiologies for autism cases with macrocephaly by describing two novel suspected pathogenic copy number variants located at 6q23.2 and 10q24.32. These findings demonstrate the phenotypic heterogeneity of autism cases associated with macrocephaly and their genetic etiologies. The clinical yield from PTEN mutation analysis is 22% and 9% from chromosomal microarray (CMA) testing within this cohort. The identification of three distinct phenotypic subgroups within macrocephaly autism patients may allow for the identification of their respective distinct genetic etiologies that to date have remained elusive. En ligne : http://dx.doi.org/10.1002/aur.1266 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=192

Support for calcium channel gene defects in autism spectrum disorders / Ake Tzu-Hui LU in Molecular Autism, (December 2012)  

Public ISBD [article]  inMolecular Autism > (December 2012) . - 9 p. Titre : Support for calcium channel gene defects in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Ake Tzu-Hui LU, Auteur ; Xiaoxian DAI, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Rita M. CANTOR, Auteur Année de publication : 2012 Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  Calcium channel genes  Common variants  Imputed SNPs  Association studies Index. décimale : PER Périodiques Résumé : BACKGROUND:Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD). Calcium channel genes (CCG) contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS) data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis.METHODS:A total of 2,176 single-nucleotide polymorphisms (SNP) (703 genotyped and 1,473 imputed) covering the genes that encode the alpha1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE) and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP). SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel.RESULTS:Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations.CONCLUSIONS:These associations support a role for common CCG SNPs in ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-3-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Support for calcium channel gene defects in autism spectrum disorders [Texte imprimé et/ou numérique] / Ake Tzu-Hui LU, Auteur ; Xiaoxian DAI, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Rita M. CANTOR, Auteur . - 2012 . - 9 p. Langues : Anglais (eng) in Molecular Autism > (December 2012) . - 9 p. Mots-clés : Autism spectrum disorders  Calcium channel genes  Common variants  Imputed SNPs  Association studies Index. décimale : PER Périodiques Résumé : BACKGROUND:Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD). Calcium channel genes (CCG) contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS) data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis.METHODS:A total of 2,176 single-nucleotide polymorphisms (SNP) (703 genotyped and 1,473 imputed) covering the genes that encode the alpha1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE) and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP). SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel.RESULTS:Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations.CONCLUSIONS:These associations support a role for common CCG SNPs in ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-3-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

The Feasibility and Outcomes of Genetic Testing for Autism and Neurodevelopmental Disorders on an Inpatient Child and Adolescent Psychiatry Service / Aaron D. BESTERMAN in Autism Research, 13-9 (September 2020)  

Public ISBD [article]  inAutism Research > 13-9 (September 2020) . - p.1450-1464 Titre : The Feasibility and Outcomes of Genetic Testing for Autism and Neurodevelopmental Disorders on an Inpatient Child and Adolescent Psychiatry Service Type de document : Texte imprimé et/ou numérique Auteurs : Aaron D. BESTERMAN, Auteur ; Joshua SADIK, Auteur ; Michael J. ENENBACH, Auteur ; Fabiola QUINTERO-RIVERA, Auteur ; Mark DEANTONIO, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur Article en page(s) : p.1450-1464 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Diagnostic genetic testing is recommended for children with autism spectrum disorder and other neurodevelopmental disorders. One approach to improve access to genetic testing is to offer it on the inpatient child and adolescent psychiatry (CAP) service. We provided medical genetics education to CAP fellows and retrospectively compared the genetic testing rates and diagnostic yield pre- and post-education. We compared demographics to similar patients who received testing on other clinical services and assessed rates of outpatient genetics follow-up post-discharge. The genetic testing rate on the inpatient CAP service was 1.6% before the educational intervention and 10.7% afterward. Genetic risk factors were identified in 4.3% of inpatients. However, 34.8% had variants of unknown significance. 39.1% of patients who received genetic testing while inpatients were underrepresented minorities, compared to 7.7% of inpatients who received genetic testing from other clinical services. 43.5% of patients were lost to outpatient genetics follow-up. We have demonstrated that it is feasible to provide medical genetics education to CAP fellows on an inpatient service, which may improve genetic testing rates. This preliminary evidence also suggests that genetic testing for inpatients may identify variants of unknown significance instead of well-known neurodevelopmental disorder risk variants. Genetic testing on an inpatient CAP service may also improve access to genetic services for underrepresented minorities, but assuring outpatient follow-up can be challenging. Lay Summary Genetic testing is recommended for children with autism and related developmental conditions. We provided genetic testing to a group of these children who were in a psychiatric hospital by teaching their doctors how it can be helpful. We identified a genetic risk factor in a small percentage of children and a possible genetic risk factor in a large percentage of children. However, many children did not end up receiving their genetic test results once they left the hospital. These results tell us that the psychiatric hospital may be a good place for children with autism and behavioral problems to get genetic testing, but that it is really important that doctors assure follow-up is feasible for all patients to receive their genetic test results once they leave the hospital. Autism Res 2020, 13: 1450–1464. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2338 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431 [article] The Feasibility and Outcomes of Genetic Testing for Autism and Neurodevelopmental Disorders on an Inpatient Child and Adolescent Psychiatry Service [Texte imprimé et/ou numérique] / Aaron D. BESTERMAN, Auteur ; Joshua SADIK, Auteur ; Michael J. ENENBACH, Auteur ; Fabiola QUINTERO-RIVERA, Auteur ; Mark DEANTONIO, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur . - p.1450-1464. Langues : Anglais (eng) in Autism Research > 13-9 (September 2020) . - p.1450-1464 Index. décimale : PER Périodiques Résumé : Diagnostic genetic testing is recommended for children with autism spectrum disorder and other neurodevelopmental disorders. One approach to improve access to genetic testing is to offer it on the inpatient child and adolescent psychiatry (CAP) service. We provided medical genetics education to CAP fellows and retrospectively compared the genetic testing rates and diagnostic yield pre- and post-education. We compared demographics to similar patients who received testing on other clinical services and assessed rates of outpatient genetics follow-up post-discharge. The genetic testing rate on the inpatient CAP service was 1.6% before the educational intervention and 10.7% afterward. Genetic risk factors were identified in 4.3% of inpatients. However, 34.8% had variants of unknown significance. 39.1% of patients who received genetic testing while inpatients were underrepresented minorities, compared to 7.7% of inpatients who received genetic testing from other clinical services. 43.5% of patients were lost to outpatient genetics follow-up. We have demonstrated that it is feasible to provide medical genetics education to CAP fellows on an inpatient service, which may improve genetic testing rates. This preliminary evidence also suggests that genetic testing for inpatients may identify variants of unknown significance instead of well-known neurodevelopmental disorder risk variants. Genetic testing on an inpatient CAP service may also improve access to genetic services for underrepresented minorities, but assuring outpatient follow-up can be challenging. Lay Summary Genetic testing is recommended for children with autism and related developmental conditions. We provided genetic testing to a group of these children who were in a psychiatric hospital by teaching their doctors how it can be helpful. We identified a genetic risk factor in a small percentage of children and a possible genetic risk factor in a large percentage of children. However, many children did not end up receiving their genetic test results once they left the hospital. These results tell us that the psychiatric hospital may be a good place for children with autism and behavioral problems to get genetic testing, but that it is really important that doctors assure follow-up is feasible for all patients to receive their genetic test results once they leave the hospital. Autism Res 2020, 13: 1450–1464. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2338 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431

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