A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case / Claudia Ismania SAMOGY-COSTA in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 13 p. Titre : A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case Type de document : texte imprimé Auteurs : Claudia Ismania SAMOGY-COSTA, Auteur ; Elisa VARELLA-BRANCO, Auteur ; Frederico MONFARDINI, Auteur ; Helen FERRAZ, Auteur ; Rodrigo Ambrósio FOCK, Auteur ; Ricardo Henrique Almeida BARBOSA, Auteur ; André Luiz Santos PESSOA, Auteur ; Ana Beatriz Alvarez PEREZ, Auteur ; N. LOURENCO, Auteur ; Maria VIBRANOVSKI, Auteur ; Ana KREPISCHI, Auteur ; Carla ROSENBERG, Auteur ; Maria Rita PASSOS-BUENO, Auteur Article en page(s) : 13 p. Langues : Anglais (eng) Mots-clés : 22q13.3 deletion syndrome  Autism spectrum disorder  Phelan-McDermid syndrome  Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype. METHODOLOGY: A total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders. RESULTS: Our data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. Increased pain tolerance (80%), hypotonia (85%), and sparse eyebrows (80%) were prominent clinical features. An atypical case diagnosed with PMS at 18 years old and IQ within the normal range is here described. Among Brazilian ASD or ID individuals referred to CNV analyses, the frequency of 22q13.3 deletion was 0.6% (5/829) and 0.61% (15/2297), respectively. Finally, renal abnormalities, lymphedema, and language impairment were found to be positively associated with deletion sizes, and the minimum deletion to cause these abnormalities is here suggested. CONCLUSIONS: This is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carrying SHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can minimize the severity of this condition. En ligne : https://dx.doi.org/10.1186/s11689-019-9273-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case [texte imprimé] / Claudia Ismania SAMOGY-COSTA, Auteur ; Elisa VARELLA-BRANCO, Auteur ; Frederico MONFARDINI, Auteur ; Helen FERRAZ, Auteur ; Rodrigo Ambrósio FOCK, Auteur ; Ricardo Henrique Almeida BARBOSA, Auteur ; André Luiz Santos PESSOA, Auteur ; Ana Beatriz Alvarez PEREZ, Auteur ; N. LOURENCO, Auteur ; Maria VIBRANOVSKI, Auteur ; Ana KREPISCHI, Auteur ; Carla ROSENBERG, Auteur ; Maria Rita PASSOS-BUENO, Auteur . - 13 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 13 p. Mots-clés : 22q13.3 deletion syndrome  Autism spectrum disorder  Phelan-McDermid syndrome  Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype. METHODOLOGY: A total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders. RESULTS: Our data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. Increased pain tolerance (80%), hypotonia (85%), and sparse eyebrows (80%) were prominent clinical features. An atypical case diagnosed with PMS at 18 years old and IQ within the normal range is here described. Among Brazilian ASD or ID individuals referred to CNV analyses, the frequency of 22q13.3 deletion was 0.6% (5/829) and 0.61% (15/2297), respectively. Finally, renal abnormalities, lymphedema, and language impairment were found to be positively associated with deletion sizes, and the minimum deletion to cause these abnormalities is here suggested. CONCLUSIONS: This is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carrying SHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can minimize the severity of this condition. En ligne : https://dx.doi.org/10.1186/s11689-019-9273-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

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 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 R. 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] / 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 R. 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 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] / 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

Identifying biomarkers and trajectories of executive functions and language development in the first 3 years of life: Design, methods, and findings of the Germina cohort study / Daniel FATORI in Development and Psychopathology, 37-5 (December 2025)  

Public ISBD [article]  inDevelopment and Psychopathology > 37-5 (December 2025) . - p.2457-2467 Titre : Identifying biomarkers and trajectories of executive functions and language development in the first 3 years of life: Design, methods, and findings of the Germina cohort study Type de document : texte imprimé Auteurs : Daniel FATORI, Auteur ; Elizabeth SHEPHARD, Auteur ; Danilo BENETTE, Auteur ; Nathalia Ferrazzo NASPOLINI, Auteur ; Grover Castro GUZMAN, Auteur ; Jaqueline Yu Ting WANG, Auteur ; Pedro TÓTOLO, Auteur ; Anthonieta Looman MAFRA, Auteur ; Caio ISAIAS, Auteur ; Davi Pereira DOS SANTOS, Auteur ; Fabiele Baldino RUSSO, Auteur ; Gerson KOBAYASHI, Auteur ; Adriana ARGEU, Auteur ; Monike TEIXEIRA, Auteur ; Ana Claudia MATTIELLO-SVERZUT, Auteur ; Maria Teresa Bechere FERNANDES, Auteur ; Danila Cristina PETIAN-ALONSO, Auteur ; Helena BRENTANI, Auteur ; Marilia SCLIAR, Auteur ; Paulo Alfonso SCHÃœROFF, Auteur ; Pedro ZUCCOLO, Auteur ; Rogério LERNER, Auteur ; Stephania GERALDINI, Auteur ; Veronica Luiza Vale EUCLYDES, Auteur ; Alicia MATIJASEVICH, Auteur ; Alline Cristina DE CAMPOS, Auteur ; André Carlos Ponce DE CARVALHO, Auteur ; André FUJITA, Auteur ; Carla R. TADDEI, Auteur ; Maria Rita PASSOS-BUENO, Auteur ; Patricia BELTRÃO-BRAGA, Auteur ; Guilherme Vanoni POLANCZYK, Auteur Article en page(s) : p.2457-2467 Langues : Anglais (eng) Mots-clés : child development  cohort study  electroencephalography  genetics  gut microbiome Index. décimale : PER Périodiques Résumé : This paper reports the methods and preliminary findings of Germina, an ongoing cohort study to identify biomarkers and trajectories of executive functions and language development in the first 3 years of life. 557 mother-infant dyads (mean age of mothers 33.7 years, 65.2% white, 48.7% male infants) have undergone baseline and are currently collecting data for other timepoints. A linear regression was used to predict baseline Bayley-III using scores derived from data-driven sparse partial least squares utilizing a multiple holdout framework of 15 domains. Significant associations were found between socioeconomic/demographic characteristics (B = 0.29), epigenetics (B = 0.11), EEG theta (B = 0.14) and beta activity (B = 0.11), and microbiome functional pathways (B = 0.08) domains, and infant development measured by the Bayley-III at T1, suggesting potential interventions to prevent impairments. En ligne : https://dx.doi.org/10.1017/S0954579425000069 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=572 [article] Identifying biomarkers and trajectories of executive functions and language development in the first 3 years of life: Design, methods, and findings of the Germina cohort study [texte imprimé] / Daniel FATORI, Auteur ; Elizabeth SHEPHARD, Auteur ; Danilo BENETTE, Auteur ; Nathalia Ferrazzo NASPOLINI, Auteur ; Grover Castro GUZMAN, Auteur ; Jaqueline Yu Ting WANG, Auteur ; Pedro TÓTOLO, Auteur ; Anthonieta Looman MAFRA, Auteur ; Caio ISAIAS, Auteur ; Davi Pereira DOS SANTOS, Auteur ; Fabiele Baldino RUSSO, Auteur ; Gerson KOBAYASHI, Auteur ; Adriana ARGEU, Auteur ; Monike TEIXEIRA, Auteur ; Ana Claudia MATTIELLO-SVERZUT, Auteur ; Maria Teresa Bechere FERNANDES, Auteur ; Danila Cristina PETIAN-ALONSO, Auteur ; Helena BRENTANI, Auteur ; Marilia SCLIAR, Auteur ; Paulo Alfonso SCHÃœROFF, Auteur ; Pedro ZUCCOLO, Auteur ; Rogério LERNER, Auteur ; Stephania GERALDINI, Auteur ; Veronica Luiza Vale EUCLYDES, Auteur ; Alicia MATIJASEVICH, Auteur ; Alline Cristina DE CAMPOS, Auteur ; André Carlos Ponce DE CARVALHO, Auteur ; André FUJITA, Auteur ; Carla R. TADDEI, Auteur ; Maria Rita PASSOS-BUENO, Auteur ; Patricia BELTRÃO-BRAGA, Auteur ; Guilherme Vanoni POLANCZYK, Auteur . - p.2457-2467. Langues : Anglais (eng) in Development and Psychopathology > 37-5 (December 2025) . - p.2457-2467 Mots-clés : child development  cohort study  electroencephalography  genetics  gut microbiome Index. décimale : PER Périodiques Résumé : This paper reports the methods and preliminary findings of Germina, an ongoing cohort study to identify biomarkers and trajectories of executive functions and language development in the first 3 years of life. 557 mother-infant dyads (mean age of mothers 33.7 years, 65.2% white, 48.7% male infants) have undergone baseline and are currently collecting data for other timepoints. A linear regression was used to predict baseline Bayley-III using scores derived from data-driven sparse partial least squares utilizing a multiple holdout framework of 15 domains. Significant associations were found between socioeconomic/demographic characteristics (B = 0.29), epigenetics (B = 0.11), EEG theta (B = 0.14) and beta activity (B = 0.11), and microbiome functional pathways (B = 0.08) domains, and infant development measured by the Bayley-III at T1, suggesting potential interventions to prevent impairments. En ligne : https://dx.doi.org/10.1017/S0954579425000069 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=572

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 Auteurs : Eduarda Morgana DA SILVA MONTENEGRO, Auteur ; Claudia Ismania 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] / Eduarda Morgana DA SILVA MONTENEGRO, Auteur ; Claudia Ismania 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)  

Permalink

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)  

Permalink

---

1 (1 - 7 / 7) Par page : 25 50 100 200