CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems / S. CHENIER in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.9 Titre : CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems Type de document : texte imprimé Auteurs : S. CHENIER, Auteur ; Grace YOON, Auteur ; Bob ARGIROPOULOS, Auteur ; Julie LAUZON, Auteur ; Rachel LAFRAMBOISE, Auteur ; Joo Wook AHN, Auteur ; Caroline Mackie OGILVIE, Auteur ; Anath C. LIONEL, Auteur ; Christian R. MARSHALL, Auteur ; Andrea K. VAAGS, Auteur ; Bita HASHEMI, Auteur ; K. BOISVERT, Auteur ; Géraldine MATHONNET, Auteur ; Frédérique TIHY, Auteur ; Joyce SO, Auteur ; Stephen SCHERER, Auteur ; Emmanuelle LEMYRE, Auteur ; Dimitri J. STAVROPOULOS, Auteur Article en page(s) : p.9 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Chd2  Developmental delay  Epilepsy  Learning disability Index. décimale : PER Périodiques Résumé : BACKGROUND: The chromodomain helicase DNA binding domain (CHD) proteins modulate gene expression via their ability to remodel chromatin structure and influence histone acetylation. Recent studies have shown that CHD2 protein plays a critical role in embryonic development, tumor suppression and survival. Like other genes encoding members of the CHD family, pathogenic mutations in the CHD2 gene are expected to be implicated in human disease. In fact, there is emerging evidence suggesting that CHD2 might contribute to a broad spectrum of neurodevelopmental disorders. Despite growing evidence, a description of the full phenotypic spectrum of this condition is lacking. METHODS: We conducted a multicentre study to identify and characterise the clinical features associated with haploinsufficiency of CHD2. Patients with deletions of this gene were identified from among broadly ascertained clinical cohorts undergoing genomic microarray analysis for developmental delay, congenital anomalies and/or autism spectrum disorder. RESULTS: Detailed clinical assessments by clinical geneticists showed recurrent clinical symptoms, including developmental delay, intellectual disability, epilepsy, behavioural problems and autism-like features without characteristic facial gestalt or brain malformations observed on magnetic resonance imaging scans. Parental analysis showed that the deletions affecting CHD2 were de novo in all four patients, and analysis of high-resolution microarray data derived from 26,826 unaffected controls showed no deletions of this gene. CONCLUSIONS: The results of this study, in addition to our review of the literature, support a causative role of CHD2 haploinsufficiency in developmental delay, intellectual disability, epilepsy and behavioural problems, with phenotypic variability between individuals. En ligne : http://dx.doi.org/10.1186/1866-1955-6-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346 [article] CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems [texte imprimé] / S. CHENIER, Auteur ; Grace YOON, Auteur ; Bob ARGIROPOULOS, Auteur ; Julie LAUZON, Auteur ; Rachel LAFRAMBOISE, Auteur ; Joo Wook AHN, Auteur ; Caroline Mackie OGILVIE, Auteur ; Anath C. LIONEL, Auteur ; Christian R. MARSHALL, Auteur ; Andrea K. VAAGS, Auteur ; Bita HASHEMI, Auteur ; K. BOISVERT, Auteur ; Géraldine MATHONNET, Auteur ; Frédérique TIHY, Auteur ; Joyce SO, Auteur ; Stephen SCHERER, Auteur ; Emmanuelle LEMYRE, Auteur ; Dimitri J. STAVROPOULOS, Auteur . - p.9. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.9 Mots-clés : Autism spectrum disorder  Chd2  Developmental delay  Epilepsy  Learning disability Index. décimale : PER Périodiques Résumé : BACKGROUND: The chromodomain helicase DNA binding domain (CHD) proteins modulate gene expression via their ability to remodel chromatin structure and influence histone acetylation. Recent studies have shown that CHD2 protein plays a critical role in embryonic development, tumor suppression and survival. Like other genes encoding members of the CHD family, pathogenic mutations in the CHD2 gene are expected to be implicated in human disease. In fact, there is emerging evidence suggesting that CHD2 might contribute to a broad spectrum of neurodevelopmental disorders. Despite growing evidence, a description of the full phenotypic spectrum of this condition is lacking. METHODS: We conducted a multicentre study to identify and characterise the clinical features associated with haploinsufficiency of CHD2. Patients with deletions of this gene were identified from among broadly ascertained clinical cohorts undergoing genomic microarray analysis for developmental delay, congenital anomalies and/or autism spectrum disorder. RESULTS: Detailed clinical assessments by clinical geneticists showed recurrent clinical symptoms, including developmental delay, intellectual disability, epilepsy, behavioural problems and autism-like features without characteristic facial gestalt or brain malformations observed on magnetic resonance imaging scans. Parental analysis showed that the deletions affecting CHD2 were de novo in all four patients, and analysis of high-resolution microarray data derived from 26,826 unaffected controls showed no deletions of this gene. CONCLUSIONS: The results of this study, in addition to our review of the literature, support a causative role of CHD2 haploinsufficiency in developmental delay, intellectual disability, epilepsy and behavioural problems, with phenotypic variability between individuals. En ligne : http://dx.doi.org/10.1186/1866-1955-6-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346

Copy Number Variation in Autism Spectrum Disorders / Christian R. MARSHALL

Public ISBD in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM Titre : Copy Number Variation in Autism Spectrum Disorders Type de document : texte imprimé Auteurs : Christian R. MARSHALL, Auteur ; Anath C. LIONEL, Auteur ; Stephen SCHERER, Auteur Année de publication : 2013 Importance : p.145-154 Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Résumé : It is well established that a significant proportion of the risk underlying autism spectrum disorders (ASD) is genetic. The rapid advancement of high-resolution genome scanning technologies has led to several reproducible findings that are beginning to uncover the genetic architecture of ASD. An identifiable genetic etiology exists in approximately 15% of individuals with ASD, with a large proportion of this currently attributable to copy number variations (CNVs). A recent focus of research has been to identify rare (lt; 0.1% frequency), but apparently highly penetrant, CNVs for candidate ASD-risk gene discovery. This strategy has yielded identification of rare de novo or inherited CNVs in upwards of 10% of cases, implicating hundreds of risk genes in ASD, many of which are involved in synaptic function. The discovery of these highly penetrant susceptibility genes has immediate impact on genetic diagnostic testing while also uncovering pathways amenable for therapeutic intervention. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=189 in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM Copy Number Variation in Autism Spectrum Disorders [texte imprimé] / Christian R. MARSHALL, Auteur ; Anath C. LIONEL, Auteur ; Stephen SCHERER, Auteur . - 2013 . - p.145-154. Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Résumé : It is well established that a significant proportion of the risk underlying autism spectrum disorders (ASD) is genetic. The rapid advancement of high-resolution genome scanning technologies has led to several reproducible findings that are beginning to uncover the genetic architecture of ASD. An identifiable genetic etiology exists in approximately 15% of individuals with ASD, with a large proportion of this currently attributable to copy number variations (CNVs). A recent focus of research has been to identify rare (lt; 0.1% frequency), but apparently highly penetrant, CNVs for candidate ASD-risk gene discovery. This strategy has yielded identification of rare de novo or inherited CNVs in upwards of 10% of cases, implicating hundreds of risk genes in ASD, many of which are involved in synaptic function. The discovery of these highly penetrant susceptibility genes has immediate impact on genetic diagnostic testing while also uncovering pathways amenable for therapeutic intervention. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=189

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Erratum: A genotype resource for postmortem brain samples from the Autism Tissue Program / Richard F. WINTLE in Autism Research, 4-4 (August 2011)  

Public ISBD [article]  inAutism Research > 4-4 (August 2011) . - p.314 Titre : Erratum: A genotype resource for postmortem brain samples from the Autism Tissue Program Type de document : texte imprimé Auteurs : Richard F. WINTLE, Auteur ; Anath C. LIONEL, Auteur ; Pingzhao HU, Auteur ; Stephen D. GINSBERG, Auteur ; Dalila PINTO, Auteur ; Bhooma THIRUVAHINDRAPDURAM, Auteur ; John WEI, Auteur ; Christian R. MARSHALL, Auteur ; Jane PICKETT, Auteur ; Edwin H. Jr COOK, Auteur ; Stephen SCHERER, Auteur Année de publication : 2011 Article en page(s) : p.314 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.211 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=142 [article] Erratum: A genotype resource for postmortem brain samples from the Autism Tissue Program [texte imprimé] / Richard F. WINTLE, Auteur ; Anath C. LIONEL, Auteur ; Pingzhao HU, Auteur ; Stephen D. GINSBERG, Auteur ; Dalila PINTO, Auteur ; Bhooma THIRUVAHINDRAPDURAM, Auteur ; John WEI, Auteur ; Christian R. MARSHALL, Auteur ; Jane PICKETT, Auteur ; Edwin H. Jr COOK, Auteur ; Stephen SCHERER, Auteur . - 2011 . - p.314. Langues : Anglais (eng) in Autism Research > 4-4 (August 2011) . - p.314 Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.211 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=142

A genotype resource for postmortem brain samples from the Autism Tissue Program / Richard F. WINTLE in Autism Research, 4-2 (April 2011)  

Public ISBD [article]  inAutism Research > 4-2 (April 2011) . - p.89-97 Titre : A genotype resource for postmortem brain samples from the Autism Tissue Program Type de document : texte imprimé Auteurs : Richard F. WINTLE, Auteur ; Anath C. LIONEL, Auteur ; Pingzhao HU, Auteur ; Stephen D. GINSBERG, Auteur ; Dalila PINTO, Auteur ; Bhooma THIRUVAHINDRAPDURAM, Auteur ; John WEI, Auteur ; Christian R. MARSHALL, Auteur ; Jane PICKETT, Auteur ; Edwin H. Jr COOK, Auteur ; Stephen SCHERER, Auteur Année de publication : 2011 Article en page(s) : p.89-97 Langues : Anglais (eng) Mots-clés : autism  autism spectrum disorder  brain  brodmann area 19  copy number variation  genome-wide  microarray  single nucleotide polymorphism Index. décimale : PER Périodiques Résumé : The Autism Tissue Program (ATP), a science program of Autism Speaks, provides researchers with access to well-characterized postmortem brain tissues. Researchers access these tissues through a peer-reviewed, project-based approval process, and obtain related clinical information from a secure, online informatics portal. However, few of these samples have DNA banked from other sources (such as a blood sample from the same individual), hindering genotype–phenotype correlation and interpretation of gene expression data derived from the banked brain tissue. Here, we describe an initiative to extract DNA from Brodmann Area 19, and genotype these samples using both the Affymetrix Genome-Wide Human SNP Array 6.0 and the Illumina Human1M-Duo DNA Analysis BeadChip genome-wide microarray technologies. We additionally verify reported gender, and infer ethnic background from the single nucleotide polymorphism data. We have also used a rigorous, multiple algorithm approach to identify genomic copy number variation (CNV) from these array data. Following an initial proof of principle study using two samples, 52 experimental samples, consisting of 27 subjects with confirmed or suspected autism and related disorders, 5 subjects with cytogenetically visible duplications of 15q, 2 with epilepsy and 18 age-matched normal controls were processed, yielding high-quality genotype data in all cases. The genotype and CNV data are provided via the ATP informatics portal as a resource for the autism research community. En ligne : http://dx.doi.org/10.1002/aur.173 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121 [article] A genotype resource for postmortem brain samples from the Autism Tissue Program [texte imprimé] / Richard F. WINTLE, Auteur ; Anath C. LIONEL, Auteur ; Pingzhao HU, Auteur ; Stephen D. GINSBERG, Auteur ; Dalila PINTO, Auteur ; Bhooma THIRUVAHINDRAPDURAM, Auteur ; John WEI, Auteur ; Christian R. MARSHALL, Auteur ; Jane PICKETT, Auteur ; Edwin H. Jr COOK, Auteur ; Stephen SCHERER, Auteur . - 2011 . - p.89-97. Langues : Anglais (eng) in Autism Research > 4-2 (April 2011) . - p.89-97 Mots-clés : autism  autism spectrum disorder  brain  brodmann area 19  copy number variation  genome-wide  microarray  single nucleotide polymorphism Index. décimale : PER Périodiques Résumé : The Autism Tissue Program (ATP), a science program of Autism Speaks, provides researchers with access to well-characterized postmortem brain tissues. Researchers access these tissues through a peer-reviewed, project-based approval process, and obtain related clinical information from a secure, online informatics portal. However, few of these samples have DNA banked from other sources (such as a blood sample from the same individual), hindering genotype–phenotype correlation and interpretation of gene expression data derived from the banked brain tissue. Here, we describe an initiative to extract DNA from Brodmann Area 19, and genotype these samples using both the Affymetrix Genome-Wide Human SNP Array 6.0 and the Illumina Human1M-Duo DNA Analysis BeadChip genome-wide microarray technologies. We additionally verify reported gender, and infer ethnic background from the single nucleotide polymorphism data. We have also used a rigorous, multiple algorithm approach to identify genomic copy number variation (CNV) from these array data. Following an initial proof of principle study using two samples, 52 experimental samples, consisting of 27 subjects with confirmed or suspected autism and related disorders, 5 subjects with cytogenetically visible duplications of 15q, 2 with epilepsy and 18 age-matched normal controls were processed, yielding high-quality genotype data in all cases. The genotype and CNV data are provided via the ATP informatics portal as a resource for the autism research community. En ligne : http://dx.doi.org/10.1002/aur.173 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121

Mutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly / Marc WOODBURY-SMITH in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 59p. Titre : Mutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly Type de document : texte imprimé Auteurs : Marc WOODBURY-SMITH, Auteur ; Eric DENEAULT, Auteur ; Ryan K.C. YUEN, Auteur ; Susan WALKER, Auteur ; Mehdi ZARREI, Auteur ; Giovanna PELLECCHIA, Auteur ; Jennifer L. HOWE, Auteur ; Ny HOANG, Auteur ; Mohammed UDDIN, Auteur ; Christian R. MARSHALL, Auteur ; Christina CHRYSLER, Auteur ; Aleda THOMPSON, Auteur ; Peter SZATMARI, Auteur ; Stephen SCHERER, Auteur Article en page(s) : 59p. Langues : Anglais (eng) Mots-clés : Intellectual disability (ID)  Rab39b  RNAseq  Whole genome sequencing (WGS) Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD), a developmental disorder of early childhood onset, affects males four times more frequently than females, suggesting a role for the sex chromosomes. In this study, we describe a family with ASD in which a predicted pathogenic nonsense mutation in the X-chromosome gene RAB39B segregates with ASD phenotype. Methods: Clinical phenotyping, microarray, and whole genome sequencing (WGS) were performed on the five members of this family. Maternal and female sibling X inactivation ratio was calculated, and phase was investigated. Mutant-induced pluripotent stem cells engineered for an exon 2 nonsense mutation were generated and differentiated into cortical neurons for expression and pathway analyses. Results: Two males with an inherited RAB39B mutation both presented with macrocephaly, intellectual disability (ID), and ASD. Their female sibling with the same mutation presented with ID and a broad autism phenotype. In contrast, their transmitting mother has no neurodevelopmental diagnosis. Our investigation of phase indicated maternal preferential inactivation of the mutated allele, with no such bias observed in the female sibling. We offer the explanation that this bias in X inactivation may explain the absence of a neurocognitive phenotype in the mother. Our cellular knockout model of RAB39B revealed an impact on expression in differentiated neurons for several genes implicated in brain development and function, supported by our pathway enrichment analysis. Conclusions: Penetrance for ASD is high among males but more variable among females with RAB39B mutations. A critical role for this gene in brain development and function is demonstrated. En ligne : http://dx.doi.org/10.1186/s13229-017-0175-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331 [article] Mutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly [texte imprimé] / Marc WOODBURY-SMITH, Auteur ; Eric DENEAULT, Auteur ; Ryan K.C. YUEN, Auteur ; Susan WALKER, Auteur ; Mehdi ZARREI, Auteur ; Giovanna PELLECCHIA, Auteur ; Jennifer L. HOWE, Auteur ; Ny HOANG, Auteur ; Mohammed UDDIN, Auteur ; Christian R. MARSHALL, Auteur ; Christina CHRYSLER, Auteur ; Aleda THOMPSON, Auteur ; Peter SZATMARI, Auteur ; Stephen SCHERER, Auteur . - 59p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 59p. Mots-clés : Intellectual disability (ID)  Rab39b  RNAseq  Whole genome sequencing (WGS) Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD), a developmental disorder of early childhood onset, affects males four times more frequently than females, suggesting a role for the sex chromosomes. In this study, we describe a family with ASD in which a predicted pathogenic nonsense mutation in the X-chromosome gene RAB39B segregates with ASD phenotype. Methods: Clinical phenotyping, microarray, and whole genome sequencing (WGS) were performed on the five members of this family. Maternal and female sibling X inactivation ratio was calculated, and phase was investigated. Mutant-induced pluripotent stem cells engineered for an exon 2 nonsense mutation were generated and differentiated into cortical neurons for expression and pathway analyses. Results: Two males with an inherited RAB39B mutation both presented with macrocephaly, intellectual disability (ID), and ASD. Their female sibling with the same mutation presented with ID and a broad autism phenotype. In contrast, their transmitting mother has no neurodevelopmental diagnosis. Our investigation of phase indicated maternal preferential inactivation of the mutated allele, with no such bias observed in the female sibling. We offer the explanation that this bias in X inactivation may explain the absence of a neurocognitive phenotype in the mother. Our cellular knockout model of RAB39B revealed an impact on expression in differentiated neurons for several genes implicated in brain development and function, supported by our pathway enrichment analysis. Conclusions: Penetrance for ASD is high among males but more variable among females with RAB39B mutations. A critical role for this gene in brain development and function is demonstrated. En ligne : http://dx.doi.org/10.1186/s13229-017-0175-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331

Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders / Gregory COSTAIN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

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Recurrent duplications of the annexin A1 gene (ANXA1) in autism spectrum disorders / Catarina T. CORREIA in Molecular Autism, (April 2014)  

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Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation / MatthewJ GAZZELLONE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

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Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10 / Annisa Shui Lam MAK in Molecular Autism, 8 (2017)  

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