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

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