A CTNNA3 compound heterozygous deletion implicates a role for alphaT-catenin in susceptibility to autism spectrum disorder / Elena BACCHELLI in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.17 Titre : A CTNNA3 compound heterozygous deletion implicates a role for alphaT-catenin in susceptibility to autism spectrum disorder Type de document : texte imprimé Auteurs : Elena BACCHELLI, Auteur ; Fabiola CERONI, Auteur ; Dalila PINTO, Auteur ; Silvia LOMARTIRE, Auteur ; Maila GIANNANDREA, Auteur ; Patrizia D'ADAMO, Auteur ; Elena BONORA, Auteur ; Piero PARCHI, Auteur ; Raffaella TANCREDI, Auteur ; Agatino BATTAGLIA, Auteur ; Elena MAESTRINI, Auteur Article en page(s) : p.17 Langues : Anglais (eng) Mots-clés : Alpha T-catenin  Autism spectrum disorder (ASD)  Ctnna3  Cell adhesion  DNA copy number variants  alphaT-catenin Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a highly heritable, neurodevelopmental condition showing extreme genetic heterogeneity. While it is well established that rare genetic variation, both de novo and inherited, plays an important role in ASD risk, recent studies also support a rare recessive contribution. METHODS: We identified a compound heterozygous deletion intersecting the CTNNA3 gene, encoding alphaT-catenin, in a proband with ASD and moderate intellectual disability. The deletion breakpoints were mapped at base-pair resolution, and segregation analysis was performed. We compared the frequency of CTNNA3 exonic deletions in 2,147 ASD cases from the Autism Genome Project (AGP) study versus the frequency in 6,639 controls. Western blot analysis was performed to get a quantitative characterisation of Ctnna3 expression during early brain development in mouse. RESULTS: The CTNNA3 compound heterozygous deletion includes a coding exon, leading to a putative frameshift and premature stop codon. Segregation analysis in the family showed that the unaffected sister is heterozygote for the deletion, having only inherited the paternal deletion. While the frequency of CTNNA3 exonic deletions is not significantly different between ASD cases and controls, no homozygous or compound heterozygous exonic deletions were found in a sample of over 6,000 controls. Expression analysis of Ctnna3 in the mouse cortex and hippocampus (P0-P90) provided support for its role in the early stage of brain development. CONCLUSION: The finding of a rare compound heterozygous CTNNA3 exonic deletion segregating with ASD, the absence of CTNNA3 homozygous exonic deletions in controls and the high expression of Ctnna3 in both brain areas analysed implicate CTNNA3 in ASD susceptibility. En ligne : http://dx.doi.org/10.1186/1866-1955-6-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346 [article] A CTNNA3 compound heterozygous deletion implicates a role for alphaT-catenin in susceptibility to autism spectrum disorder [texte imprimé] / Elena BACCHELLI, Auteur ; Fabiola CERONI, Auteur ; Dalila PINTO, Auteur ; Silvia LOMARTIRE, Auteur ; Maila GIANNANDREA, Auteur ; Patrizia D'ADAMO, Auteur ; Elena BONORA, Auteur ; Piero PARCHI, Auteur ; Raffaella TANCREDI, Auteur ; Agatino BATTAGLIA, Auteur ; Elena MAESTRINI, Auteur . - p.17. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.17 Mots-clés : Alpha T-catenin  Autism spectrum disorder (ASD)  Ctnna3  Cell adhesion  DNA copy number variants  alphaT-catenin Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a highly heritable, neurodevelopmental condition showing extreme genetic heterogeneity. While it is well established that rare genetic variation, both de novo and inherited, plays an important role in ASD risk, recent studies also support a rare recessive contribution. METHODS: We identified a compound heterozygous deletion intersecting the CTNNA3 gene, encoding alphaT-catenin, in a proband with ASD and moderate intellectual disability. The deletion breakpoints were mapped at base-pair resolution, and segregation analysis was performed. We compared the frequency of CTNNA3 exonic deletions in 2,147 ASD cases from the Autism Genome Project (AGP) study versus the frequency in 6,639 controls. Western blot analysis was performed to get a quantitative characterisation of Ctnna3 expression during early brain development in mouse. RESULTS: The CTNNA3 compound heterozygous deletion includes a coding exon, leading to a putative frameshift and premature stop codon. Segregation analysis in the family showed that the unaffected sister is heterozygote for the deletion, having only inherited the paternal deletion. While the frequency of CTNNA3 exonic deletions is not significantly different between ASD cases and controls, no homozygous or compound heterozygous exonic deletions were found in a sample of over 6,000 controls. Expression analysis of Ctnna3 in the mouse cortex and hippocampus (P0-P90) provided support for its role in the early stage of brain development. CONCLUSION: The finding of a rare compound heterozygous CTNNA3 exonic deletion segregating with ASD, the absence of CTNNA3 homozygous exonic deletions in controls and the high expression of Ctnna3 in both brain areas analysed implicate CTNNA3 in ASD susceptibility. En ligne : http://dx.doi.org/10.1186/1866-1955-6-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346

A Deletion Involving CD38 and BST1 Results in a Fusion Transcript in a Patient With Autism and Asthma / Fabiola CERONI in Autism Research, 7-2 (April 2014)  

Public ISBD [article]  inAutism Research > 7-2 (April 2014) . - p.254-263 Titre : A Deletion Involving CD38 and BST1 Results in a Fusion Transcript in a Patient With Autism and Asthma Type de document : texte imprimé Auteurs : Fabiola CERONI, Auteur ; Angela SAGAR, Auteur ; Nuala H. SIMPSON, Auteur ; Alex J.T. GAWTHROPE, Auteur ; Dianne F. NEWBURY, Auteur ; Dalila PINTO, Auteur ; Sunday M. FRANCIS, Auteur ; Dorothy C. TESSMAN, Auteur ; Edwin H. Jr COOK, Auteur ; Anthony P. MONACO, Auteur ; Elena MAESTRINI, Auteur ; Alistair T. PAGNAMENTA, Auteur ; Suma JACOB, Auteur Article en page(s) : p.254-263 Mots-clés : autism  CD38  oxytocin  CNV  fusion transcript Index. décimale : PER Périodiques Résumé : CD38 encodes a ligand in the oxytocin signaling pathway. Some single nucleotide polymorphisms in this gene have been associated with low serum oxytocin levels in autism spectrum disorder (ASD) patients. Oxytocin disruption has been hypothesized to account for features of ASD, including impaired communication and social behavior, based on animal studies. Recent human studies have shown administration of oxytocin improving emotion recognition, promoting social behavior, and improving auditory processing of social stimuli in ASD patients. In addition to its role in oxytocin signaling, CD38 is involved in the regulation of calcium concentration in airway smooth muscle with impairment of CD38 being implicated in airway diseases like asthma. While a number of studies have implicated rare chromosomal deletions and duplications in helping determine genetic risk for autism, there are to our knowledge no reports describing rearrangements involving CD38 or deletions in patients with ASD. Here, we present two sisters diagnosed with autism and with features of regression—previously acquired speech lost in the second year of life. The younger sister, who also had asthma, inherited a maternal deletion of 4p15.32 that results in a BST1-CD38 fusion transcript. Their mother's deletion was mosaic and she was not affected. Although further work is required to assess functional consequences of the fusion transcript, we hypothesize that the proband's deletion may have served as a risk factor for autism that, when combined with other susceptibility variants, resulted in a more severe presentation than her sister. En ligne : http://dx.doi.org/10.1002/aur.1365 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=230 [article] A Deletion Involving CD38 and BST1 Results in a Fusion Transcript in a Patient With Autism and Asthma [texte imprimé] / Fabiola CERONI, Auteur ; Angela SAGAR, Auteur ; Nuala H. SIMPSON, Auteur ; Alex J.T. GAWTHROPE, Auteur ; Dianne F. NEWBURY, Auteur ; Dalila PINTO, Auteur ; Sunday M. FRANCIS, Auteur ; Dorothy C. TESSMAN, Auteur ; Edwin H. Jr COOK, Auteur ; Anthony P. MONACO, Auteur ; Elena MAESTRINI, Auteur ; Alistair T. PAGNAMENTA, Auteur ; Suma JACOB, Auteur . - p.254-263. in Autism Research > 7-2 (April 2014) . - p.254-263 Mots-clés : autism  CD38  oxytocin  CNV  fusion transcript Index. décimale : PER Périodiques Résumé : CD38 encodes a ligand in the oxytocin signaling pathway. Some single nucleotide polymorphisms in this gene have been associated with low serum oxytocin levels in autism spectrum disorder (ASD) patients. Oxytocin disruption has been hypothesized to account for features of ASD, including impaired communication and social behavior, based on animal studies. Recent human studies have shown administration of oxytocin improving emotion recognition, promoting social behavior, and improving auditory processing of social stimuli in ASD patients. In addition to its role in oxytocin signaling, CD38 is involved in the regulation of calcium concentration in airway smooth muscle with impairment of CD38 being implicated in airway diseases like asthma. While a number of studies have implicated rare chromosomal deletions and duplications in helping determine genetic risk for autism, there are to our knowledge no reports describing rearrangements involving CD38 or deletions in patients with ASD. Here, we present two sisters diagnosed with autism and with features of regression—previously acquired speech lost in the second year of life. The younger sister, who also had asthma, inherited a maternal deletion of 4p15.32 that results in a BST1-CD38 fusion transcript. Their mother's deletion was mosaic and she was not affected. Although further work is required to assess functional consequences of the fusion transcript, we hypothesize that the proband's deletion may have served as a risk factor for autism that, when combined with other susceptibility variants, resulted in a more severe presentation than her sister. En ligne : http://dx.doi.org/10.1002/aur.1365 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=230

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 family with autism and rare copy number variants disrupting the Duchenne/Becker muscular dystrophy gene DMD and TRPM3 / Alistair T. PAGNAMENTA in Journal of Neurodevelopmental Disorders, 3-2 (June 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-2 (June 2011) . - p.124-31 Titre : A family with autism and rare copy number variants disrupting the Duchenne/Becker muscular dystrophy gene DMD and TRPM3 Type de document : texte imprimé Auteurs : Alistair T. PAGNAMENTA, Auteur ; Richard HOLT, Auteur ; Mohammed YUSUF, Auteur ; Dalila PINTO, Auteur ; Kirsty WING, Auteur ; Catalina BETANCUR, Auteur ; Stephen SCHERER, Auteur ; Emanuela V. VOLPI, Auteur ; A.P. MONACO, Auteur Article en page(s) : p.124-31 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorder is a genetically complex and clinically heterogeneous neurodevelopmental disorder. A recent study by the Autism Genome Project (AGP) used 1M single-nucleotide polymorphism arrays to show that rare genic copy number variants (CNVs), possibly acting in tandem, play a significant role in the genetic aetiology of this condition. In this study, we describe the phenotypic and genomic characterisation of a multiplex autism family from the AGP study that was found to harbour a duplication of exons 31-44 of the Duchenne/Becker muscular dystrophy gene DMD and also a rare deletion involving exons 1-9 of TRPM3. Further characterisation of these extremely rare CNVs was carried out using quantitative PCR, fluorescent in situ hybridisation, long-range PCR amplification and sequencing of junction fragments. The maternal chrX:32,097,213-32,321,945 tandem duplication and paternal chr9:72,480,413-73,064,196 deletion (NCBI build 36 coordinates) were transmitted to both affected boys, potentially signifying a multi-hit mechanism. The DMD reading frame rule predicts a Becker phenotype, characterised by later onset and milder symptoms. When last evaluated, neither child had developed signs of muscular dystrophy. These data are consistent with a degree of comorbidity between autism and muscular dystrophy and suggest that genomic background as well as the position of the mutation within the DMD gene may impact on the neurological correlates of Duchenne/Becker muscular dystrophy. Finally, communicating unexpected findings such as these back to families raises a number of ethical questions, which are discussed. En ligne : http://dx.doi.org/10.1007/s11689-011-9076-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] A family with autism and rare copy number variants disrupting the Duchenne/Becker muscular dystrophy gene DMD and TRPM3 [texte imprimé] / Alistair T. PAGNAMENTA, Auteur ; Richard HOLT, Auteur ; Mohammed YUSUF, Auteur ; Dalila PINTO, Auteur ; Kirsty WING, Auteur ; Catalina BETANCUR, Auteur ; Stephen SCHERER, Auteur ; Emanuela V. VOLPI, Auteur ; A.P. MONACO, Auteur . - p.124-31. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-2 (June 2011) . - p.124-31 Index. décimale : PER Périodiques Résumé : Autism spectrum disorder is a genetically complex and clinically heterogeneous neurodevelopmental disorder. A recent study by the Autism Genome Project (AGP) used 1M single-nucleotide polymorphism arrays to show that rare genic copy number variants (CNVs), possibly acting in tandem, play a significant role in the genetic aetiology of this condition. In this study, we describe the phenotypic and genomic characterisation of a multiplex autism family from the AGP study that was found to harbour a duplication of exons 31-44 of the Duchenne/Becker muscular dystrophy gene DMD and also a rare deletion involving exons 1-9 of TRPM3. Further characterisation of these extremely rare CNVs was carried out using quantitative PCR, fluorescent in situ hybridisation, long-range PCR amplification and sequencing of junction fragments. The maternal chrX:32,097,213-32,321,945 tandem duplication and paternal chr9:72,480,413-73,064,196 deletion (NCBI build 36 coordinates) were transmitted to both affected boys, potentially signifying a multi-hit mechanism. The DMD reading frame rule predicts a Becker phenotype, characterised by later onset and milder symptoms. When last evaluated, neither child had developed signs of muscular dystrophy. These data are consistent with a degree of comorbidity between autism and muscular dystrophy and suggest that genomic background as well as the position of the mutation within the DMD gene may impact on the neurological correlates of Duchenne/Becker muscular dystrophy. Finally, communicating unexpected findings such as these back to families raises a number of ethical questions, which are discussed. En ligne : http://dx.doi.org/10.1007/s11689-011-9076-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

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

Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism / Veronica J. VIELAND in Journal of Neurodevelopmental Disorders, 3-2 (June 2011)  

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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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The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses / Joseph D. BUXBAUM in Molecular Autism, (May 2014)  

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