Burden of Rare Copy Number Variants in Microcephaly: A Brazilian Cohort of 185 Microcephalic Patients and Review of the Literature / Giovanna Cantini TOLEZANO in Journal of Autism and Developmental Disorders, 54-3 (March 2024)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 54-3 (March 2024) . - p.1181-1212 Titre : Burden of Rare Copy Number Variants in Microcephaly: A Brazilian Cohort of 185 Microcephalic Patients and Review of the Literature Type de document : Texte imprimé et/ou numérique Auteurs : Giovanna Cantini TOLEZANO, Auteur ; Giovanna Civitate BASTOS, Auteur ; Silvia Souza DA COSTA, Auteur ; Bruna Lucheze FREIRE, Auteur ; Thais Kataoka HOMMA, Auteur ; Rachel Sayuri HONJO, Auteur ; Guilherme Lopes YAMAMOTO, Auteur ; Maria Rita PASSOS-BUENO, Auteur ; Celia Priszkulnik KOIFFMANN, Auteur ; Chong Ae KIM, Auteur ; Angela Maria VIANNA-MORGANTE, Auteur ; Alexander Augusto DE LIMA JORGE, Auteur ; Débora Romeo BERTOLA, Auteur ; Carla ROSENBERG, Auteur ; Ana Cristina Victorino KREPISCHI, Auteur Article en page(s) : p.1181-1212 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Microcephaly presents heterogeneous genetic etiology linked to several neurodevelopmental disorders (NDD). Copy number variants (CNVs) are a causal mechanism of microcephaly whose investigation is a crucial step for unraveling its molecular basis. Our purpose was to investigate the burden of rare CNVs in microcephalic individuals and to review genes and CNV syndromes associated with microcephaly. We performed chromosomal microarray analysis (CMA) in 185 Brazilian patients with microcephaly and evaluated microcephalic patients carrying<200 kb CNVs documented in the DECIPHER database. Additionally, we reviewed known genes and CNV syndromes causally linked to microcephaly through the PubMed, OMIM, DECIPHER, and ClinGen databases. Rare clinically relevant CNVs were detected in 39 out of the 185 Brazilian patients investigated by CMA (21%). In 31 among the 60 DECIPHER patients carrying<200 kb CNVs, at least one known microcephaly gene was observed. Overall, four gene sets implicated in microcephaly were disclosed: known microcephaly genes; genes with supporting evidence of association with microcephaly; known macrocephaly genes; and novel candidates, including OTUD7A, BBC3, CNTN6, and NAA15. In the review, we compiled 957 known microcephaly genes and 58 genomic CNV loci, comprising 13 duplications and 50 deletions, which have already been associated with clinical findings including microcephaly. We reviewed genes and CNV syndromes previously associated with microcephaly, reinforced the high CMA diagnostic yield for this condition, pinpointed novel candidate loci linked to microcephaly deserving further evaluation, and provided a useful resource for future research on the field of neurodevelopment. En ligne : https://doi.org/10.1007/s10803-022-05853-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=524 [article] Burden of Rare Copy Number Variants in Microcephaly: A Brazilian Cohort of 185 Microcephalic Patients and Review of the Literature [Texte imprimé et/ou numérique] / Giovanna Cantini TOLEZANO, Auteur ; Giovanna Civitate BASTOS, Auteur ; Silvia Souza DA COSTA, Auteur ; Bruna Lucheze FREIRE, Auteur ; Thais Kataoka HOMMA, Auteur ; Rachel Sayuri HONJO, Auteur ; Guilherme Lopes YAMAMOTO, Auteur ; Maria Rita PASSOS-BUENO, Auteur ; Celia Priszkulnik KOIFFMANN, Auteur ; Chong Ae KIM, Auteur ; Angela Maria VIANNA-MORGANTE, Auteur ; Alexander Augusto DE LIMA JORGE, Auteur ; Débora Romeo BERTOLA, Auteur ; Carla ROSENBERG, Auteur ; Ana Cristina Victorino KREPISCHI, Auteur . - p.1181-1212. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 54-3 (March 2024) . - p.1181-1212 Index. décimale : PER Périodiques Résumé : Microcephaly presents heterogeneous genetic etiology linked to several neurodevelopmental disorders (NDD). Copy number variants (CNVs) are a causal mechanism of microcephaly whose investigation is a crucial step for unraveling its molecular basis. Our purpose was to investigate the burden of rare CNVs in microcephalic individuals and to review genes and CNV syndromes associated with microcephaly. We performed chromosomal microarray analysis (CMA) in 185 Brazilian patients with microcephaly and evaluated microcephalic patients carrying<200 kb CNVs documented in the DECIPHER database. Additionally, we reviewed known genes and CNV syndromes causally linked to microcephaly through the PubMed, OMIM, DECIPHER, and ClinGen databases. Rare clinically relevant CNVs were detected in 39 out of the 185 Brazilian patients investigated by CMA (21%). In 31 among the 60 DECIPHER patients carrying<200 kb CNVs, at least one known microcephaly gene was observed. Overall, four gene sets implicated in microcephaly were disclosed: known microcephaly genes; genes with supporting evidence of association with microcephaly; known macrocephaly genes; and novel candidates, including OTUD7A, BBC3, CNTN6, and NAA15. In the review, we compiled 957 known microcephaly genes and 58 genomic CNV loci, comprising 13 duplications and 50 deletions, which have already been associated with clinical findings including microcephaly. We reviewed genes and CNV syndromes previously associated with microcephaly, reinforced the high CMA diagnostic yield for this condition, pinpointed novel candidate loci linked to microcephaly deserving further evaluation, and provided a useful resource for future research on the field of neurodevelopment. En ligne : https://doi.org/10.1007/s10803-022-05853-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=524

Detection of small copy number variations (CNVs) in autism spectrum disorder (ASD) by custom array comparative genomic hybridization (aCGH) / Eloisa S. MOREIRA in Research in Autism Spectrum Disorders, 23 (March 2016)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 23 (March 2016) . - p.145-151 Titre : Detection of small copy number variations (CNVs) in autism spectrum disorder (ASD) by custom array comparative genomic hybridization (aCGH) Type de document : Texte imprimé et/ou numérique Auteurs : Eloisa S. MOREIRA, Auteur ; Isabela M. W. SILVA, Auteur ; Naila LOURENÇO, Auteur ; Danielle P. MOREIRA, Auteur ; Cintia M. RIBEIRO, Auteur ; Ana Luiza B. MARTINS, Auteur ; Karina GRIESI-OLIVEIRA, Auteur ; Monize LAZAR, Auteur ; Silvia S. COSTA, Auteur ; Michel S. NASLAVSKY, Auteur ; Kátia M. ROCHA, Auteur ; Meire AGUENA, Auteur ; Agnes C. FETT-CONTE, Auteur ; Mayana ZATZ, Auteur ; Carla ROSENBERG, Auteur ; Elaine C. ZACHI, Auteur ; Débora R. BERTOLA, Auteur ; Estevão VADASZ, Auteur ; Maria Rita PASSOS-BUENO, Auteur Article en page(s) : p.145-151 Langues : Anglais (eng) Mots-clés : Autism  Copy number variation  Comparative genomic hybridization  Neurodevelopmental disorder  MBD2  SLC17A6 Index. décimale : PER Périodiques Résumé : Abstract Autism spectrum disorder (ASD) has a strong genetic basis and advances in genomic scanning methods have resulted in the identification of the underlying alterations in about 30% of the cases. The overwhelming majority of these alterations are either sequencing variants or large copy number variations (CNVs). In this pilot study, we tested whether the use of a customized array comparative genomic hybridization (aCGH), targeting exons of 269 ASD candidate genes, would allow the identification of small potentially pathogenic CNVs (<100 Kb). We detected 10 rare, potentially pathogenic CNVs in nine out of 98 patients with idiopathic ASD, and none of 200 Brazilian controls. Two out of five CNVs identified among the non-syndromic cases, involving the genes MBD2 and SLC17A6, were smaller than 100 Kb. In a subsequent screening of other 407 patients and 350 non-affected controls for CNVs involving SLC17A6, a gene without previous documentation in the literature of involvement with neurodevelopmental disorders, we found intragenic duplications in another proband but also in five controls. Of note, a commercial 500 K SNP-array did not detect the smallest gains in SLC17A6. Our results suggest that small CNVs contribute to the etiology of ASD and that customized CGH array has significant potential to improve the sensitivity for detecting this class of alterations. En ligne : http://dx.doi.org/10.1016/j.rasd.2015.12.012 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282 [article] Detection of small copy number variations (CNVs) in autism spectrum disorder (ASD) by custom array comparative genomic hybridization (aCGH) [Texte imprimé et/ou numérique] / Eloisa S. MOREIRA, Auteur ; Isabela M. W. SILVA, Auteur ; Naila LOURENÇO, Auteur ; Danielle P. MOREIRA, Auteur ; Cintia M. RIBEIRO, Auteur ; Ana Luiza B. MARTINS, Auteur ; Karina GRIESI-OLIVEIRA, Auteur ; Monize LAZAR, Auteur ; Silvia S. COSTA, Auteur ; Michel S. NASLAVSKY, Auteur ; Kátia M. ROCHA, Auteur ; Meire AGUENA, Auteur ; Agnes C. FETT-CONTE, Auteur ; Mayana ZATZ, Auteur ; Carla ROSENBERG, Auteur ; Elaine C. ZACHI, Auteur ; Débora R. BERTOLA, Auteur ; Estevão VADASZ, Auteur ; Maria Rita PASSOS-BUENO, Auteur . - p.145-151. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 23 (March 2016) . - p.145-151 Mots-clés : Autism  Copy number variation  Comparative genomic hybridization  Neurodevelopmental disorder  MBD2  SLC17A6 Index. décimale : PER Périodiques Résumé : Abstract Autism spectrum disorder (ASD) has a strong genetic basis and advances in genomic scanning methods have resulted in the identification of the underlying alterations in about 30% of the cases. The overwhelming majority of these alterations are either sequencing variants or large copy number variations (CNVs). In this pilot study, we tested whether the use of a customized array comparative genomic hybridization (aCGH), targeting exons of 269 ASD candidate genes, would allow the identification of small potentially pathogenic CNVs (<100 Kb). We detected 10 rare, potentially pathogenic CNVs in nine out of 98 patients with idiopathic ASD, and none of 200 Brazilian controls. Two out of five CNVs identified among the non-syndromic cases, involving the genes MBD2 and SLC17A6, were smaller than 100 Kb. In a subsequent screening of other 407 patients and 350 non-affected controls for CNVs involving SLC17A6, a gene without previous documentation in the literature of involvement with neurodevelopmental disorders, we found intragenic duplications in another proband but also in five controls. Of note, a commercial 500 K SNP-array did not detect the smallest gains in SLC17A6. Our results suggest that small CNVs contribute to the etiology of ASD and that customized CGH array has significant potential to improve the sensitivity for detecting this class of alterations. En ligne : http://dx.doi.org/10.1016/j.rasd.2015.12.012 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282

Meta-Analyses Support Previous and Novel Autism Candidate Genes: Outcomes of an Unexplored Brazilian Cohort / Eduarda Morgana DA SILVA MONTENEGRO in Autism Research, 13-2 (February 2020)  

Public ISBD [article]  inAutism Research > 13-2 (February 2020) . - p.199-206 Titre : Meta-Analyses Support Previous and Novel Autism Candidate Genes: Outcomes of an Unexplored Brazilian Cohort Type de document : Texte imprimé et/ou numérique Auteurs : Eduarda Morgana DA SILVA MONTENEGRO, Auteur ; Claudia Samogy COSTA, Auteur ; Gabriele CAMPOS, Auteur ; Marilia SCLIAR, Auteur ; Tatiana Ferreira DE ALMEIDA, Auteur ; Elaine Cristina ZACHI, Auteur ; Isabela Maya Wahys SILVA, Auteur ; Ada J. S. CHAN, Auteur ; Mehdi ZARREI, Auteur ; Naila C. V. LOURENCO, Auteur ; Guilherme Lopes YAMAMOTO, Auteur ; Stephen SCHERER, Auteur ; Maria Rita PASSOS-BUENO, Auteur Article en page(s) : p.199-206 Langues : Anglais (eng) Mots-clés : Prpf8  Rmb14  Ddd  Mssng  Ssc Index. décimale : PER Périodiques Résumé : Large genomic databases of neurodevelopmental disorders (NDD) are helpful resources of genomic variations in complex and heterogeneous conditions, as Autism Spectrum Disorder (ASD). We evaluated the role of rare copy number variations (CNVs) and exonic de novo variants, in a molecularly unexplored Brazilian cohort of 30 ASD trios (n = 90), by performing a meta-analysis of our findings in more than 20,000 patients from NDD cohorts. We identified three pathogenic CNVs: two duplications on 1q21 and 17p13, and one deletion on 4q35. CNVs meta-analysis (n = 8,688 cases and n = 3,591 controls) confirmed 1q21 relevance by identifying duplications in other 16 ASD patients. Exome analysis led the identification of seven de novo variants in ASD genes (SFARI list): three loss-of-function pathogenic variants in CUL3, CACNA1H, and SHANK3; one missense pathogenic variant in KCNB1; and three deleterious missense variants in ATP10A, ANKS1B, and DOCK1. From the remaining 12 de novo variants in non-previous ASD genes, we prioritized PRPF8 and RBM14. Meta-analysis (n = 13,754 probands; n = 2,299 controls) identified six and two additional patients with validated de novo variants in PRPF8 and RBM14, respectively. By comparing the de novo variants with a previously established mutational rate model, PRPF8 showed nominal significance before multiple test correction (P = 0.039, P-value adjusted = 0.079, binomial test), suggesting its relevance to ASD. Approximately 60% of our patients presented comorbidities, and the diagnostic yield was estimated in 23% (7/30: three pathogenic CNVs and four pathogenic de novo variants). Our uncharacterized Brazilian cohort with tetra-hybrid ethnic composition was a valuable resource to validate and identify possible novel candidate loci. Autism Res 2020, 13: 199-206. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We believed that to study an unexplored autistic population, such as the Brazilian, could help to find novel genes for autism. In order to test this idea, with our limited budget, we compared candidate genes obtained from genomic analyses of 30 children and their parents, with those of more than 20,000 individuals from international studies. Happily, we identified a genetic cause in 23% of our patients and suggest a possible novel candidate gene for autism (PRPF8). En ligne : http://dx.doi.org/10.1002/aur.2238 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=420 [article] Meta-Analyses Support Previous and Novel Autism Candidate Genes: Outcomes of an Unexplored Brazilian Cohort [Texte imprimé et/ou numérique] / Eduarda Morgana DA SILVA MONTENEGRO, Auteur ; Claudia Samogy COSTA, Auteur ; Gabriele CAMPOS, Auteur ; Marilia SCLIAR, Auteur ; Tatiana Ferreira DE ALMEIDA, Auteur ; Elaine Cristina ZACHI, Auteur ; Isabela Maya Wahys SILVA, Auteur ; Ada J. S. CHAN, Auteur ; Mehdi ZARREI, Auteur ; Naila C. V. LOURENCO, Auteur ; Guilherme Lopes YAMAMOTO, Auteur ; Stephen SCHERER, Auteur ; Maria Rita PASSOS-BUENO, Auteur . - p.199-206. Langues : Anglais (eng) in Autism Research > 13-2 (February 2020) . - p.199-206 Mots-clés : Prpf8  Rmb14  Ddd  Mssng  Ssc Index. décimale : PER Périodiques Résumé : Large genomic databases of neurodevelopmental disorders (NDD) are helpful resources of genomic variations in complex and heterogeneous conditions, as Autism Spectrum Disorder (ASD). We evaluated the role of rare copy number variations (CNVs) and exonic de novo variants, in a molecularly unexplored Brazilian cohort of 30 ASD trios (n = 90), by performing a meta-analysis of our findings in more than 20,000 patients from NDD cohorts. We identified three pathogenic CNVs: two duplications on 1q21 and 17p13, and one deletion on 4q35. CNVs meta-analysis (n = 8,688 cases and n = 3,591 controls) confirmed 1q21 relevance by identifying duplications in other 16 ASD patients. Exome analysis led the identification of seven de novo variants in ASD genes (SFARI list): three loss-of-function pathogenic variants in CUL3, CACNA1H, and SHANK3; one missense pathogenic variant in KCNB1; and three deleterious missense variants in ATP10A, ANKS1B, and DOCK1. From the remaining 12 de novo variants in non-previous ASD genes, we prioritized PRPF8 and RBM14. Meta-analysis (n = 13,754 probands; n = 2,299 controls) identified six and two additional patients with validated de novo variants in PRPF8 and RBM14, respectively. By comparing the de novo variants with a previously established mutational rate model, PRPF8 showed nominal significance before multiple test correction (P = 0.039, P-value adjusted = 0.079, binomial test), suggesting its relevance to ASD. Approximately 60% of our patients presented comorbidities, and the diagnostic yield was estimated in 23% (7/30: three pathogenic CNVs and four pathogenic de novo variants). Our uncharacterized Brazilian cohort with tetra-hybrid ethnic composition was a valuable resource to validate and identify possible novel candidate loci. Autism Res 2020, 13: 199-206. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We believed that to study an unexplored autistic population, such as the Brazilian, could help to find novel genes for autism. In order to test this idea, with our limited budget, we compared candidate genes obtained from genomic analyses of 30 children and their parents, with those of more than 20,000 individuals from international studies. Happily, we identified a genetic cause in 23% of our patients and suggest a possible novel candidate gene for autism (PRPF8). En ligne : http://dx.doi.org/10.1002/aur.2238 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=420

Stem Cells as a Good Tool to Investigate Dysregulated Biological Systems in Autism Spectrum Disorders / Karina GRIESI-OLIVEIRA in Autism Research, 6-5 (October 2013)  

Public ISBD [article]  inAutism Research > 6-5 (October 2013) . - p.354-361 Titre : Stem Cells as a Good Tool to Investigate Dysregulated Biological Systems in Autism Spectrum Disorders Type de document : Texte imprimé et/ou numérique Auteurs : Karina GRIESI-OLIVEIRA, Auteur ; Daniele Yumi SUNAGA, Auteur ; Lucas ALVIZI, Auteur ; Estevão VADASZ, Auteur ; Maria Rita PASSOS-BUENO, Auteur Article en page(s) : p.354-361 Langues : Anglais (eng) Mots-clés : expression studies  androgen signaling  CHD8  stem cells of human exfoliated deciduous teeth Index. décimale : PER Périodiques Résumé : Identification of the causes of autism spectrum disorders (ASDs) is hampered by their genetic heterogeneity; however, the different genetic alterations leading to ASD seem to be implicated in the disturbance of common molecular pathways or biological processes. In this scenario, the search for differentially expressed genes (DEGs) between ASD patients and controls is a good alternative to identify the molecular etiology of such disorders. Here, we employed genome-wide expression analysis to compare the transcriptome of stem cells of human exfoliated deciduous teeth (SHEDs) of idiopathic autistic patients (n?=?7) and control samples (n?=?6). Nearly half of the 683 identified DEGs are expressed in the brain (P?=?0.003), and a significant number of them are involved in mechanisms previously associated with ASD such as protein synthesis, cytoskeleton regulation, cellular adhesion and alternative splicing, which validate the use of SHEDs to disentangle the causes of autism. Autistic patients also presented overexpression of genes regulated by androgen receptor (AR), and AR itself, which in turn interacts with CHD8 (chromodomain helicase DNA binding protein 8), a gene recently shown to be associated with the cause of autism and found to be upregulated in some patients tested here. These data provide a rationale for the mechanisms through which CHD8 leads to these diseases. In summary, our results suggest that ASD share deregulated pathways and revealed that SHEDs represent an alternative cell source to be used in the understanding of the biological mechanisms involved in the etiology of ASD. En ligne : http://dx.doi.org/10.1002/aur.1296 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=218 [article] Stem Cells as a Good Tool to Investigate Dysregulated Biological Systems in Autism Spectrum Disorders [Texte imprimé et/ou numérique] / Karina GRIESI-OLIVEIRA, Auteur ; Daniele Yumi SUNAGA, Auteur ; Lucas ALVIZI, Auteur ; Estevão VADASZ, Auteur ; Maria Rita PASSOS-BUENO, Auteur . - p.354-361. Langues : Anglais (eng) in Autism Research > 6-5 (October 2013) . - p.354-361 Mots-clés : expression studies  androgen signaling  CHD8  stem cells of human exfoliated deciduous teeth Index. décimale : PER Périodiques Résumé : Identification of the causes of autism spectrum disorders (ASDs) is hampered by their genetic heterogeneity; however, the different genetic alterations leading to ASD seem to be implicated in the disturbance of common molecular pathways or biological processes. In this scenario, the search for differentially expressed genes (DEGs) between ASD patients and controls is a good alternative to identify the molecular etiology of such disorders. Here, we employed genome-wide expression analysis to compare the transcriptome of stem cells of human exfoliated deciduous teeth (SHEDs) of idiopathic autistic patients (n?=?7) and control samples (n?=?6). Nearly half of the 683 identified DEGs are expressed in the brain (P?=?0.003), and a significant number of them are involved in mechanisms previously associated with ASD such as protein synthesis, cytoskeleton regulation, cellular adhesion and alternative splicing, which validate the use of SHEDs to disentangle the causes of autism. Autistic patients also presented overexpression of genes regulated by androgen receptor (AR), and AR itself, which in turn interacts with CHD8 (chromodomain helicase DNA binding protein 8), a gene recently shown to be associated with the cause of autism and found to be upregulated in some patients tested here. These data provide a rationale for the mechanisms through which CHD8 leads to these diseases. In summary, our results suggest that ASD share deregulated pathways and revealed that SHEDs represent an alternative cell source to be used in the understanding of the biological mechanisms involved in the etiology of ASD. En ligne : http://dx.doi.org/10.1002/aur.1296 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=218

Stem Cells as a Good Tool to Investigate Dysregulated Biological Systems in Autism Spectrum Disorders / Karina GRIESI-OLIVEIRA in Autism Research, 8-1 (February 2015)  

Public ISBD [article]  inAutism Research > 8-1 (February 2015) . - p.121-121 Titre : Stem Cells as a Good Tool to Investigate Dysregulated Biological Systems in Autism Spectrum Disorders Type de document : Texte imprimé et/ou numérique Auteurs : Karina GRIESI-OLIVEIRA, Auteur ; Daniele Yumi SUNAGA, Auteur ; Lucas Alvizi CRUZ, Auteur ; Estevão VADASZ, Auteur ; Maria Rita PASSOS-BUENO, Auteur Article en page(s) : p.121-121 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.1330 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=256 [article] Stem Cells as a Good Tool to Investigate Dysregulated Biological Systems in Autism Spectrum Disorders [Texte imprimé et/ou numérique] / Karina GRIESI-OLIVEIRA, Auteur ; Daniele Yumi SUNAGA, Auteur ; Lucas Alvizi CRUZ, Auteur ; Estevão VADASZ, Auteur ; Maria Rita PASSOS-BUENO, Auteur . - p.121-121. Langues : Anglais (eng) in Autism Research > 8-1 (February 2015) . - p.121-121 Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.1330 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=256

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