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 et/ou numérique Auteurs : Elena BACCHELLI, Auteur ; Fabiola CERONI, Auteur ; D. PINTO, Auteur ; S. LOMARTIRE, Auteur ; M. GIANNANDREA, Auteur ; P. D'ADAMO, Auteur ; Elena BONORA, Auteur ; P. PARCHI, Auteur ; Raffaella TANCREDI, Auteur ; A. BATTAGLIA, Auteur ; E. 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 et/ou numérique] / Elena BACCHELLI, Auteur ; Fabiola CERONI, Auteur ; D. PINTO, Auteur ; S. LOMARTIRE, Auteur ; M. GIANNANDREA, Auteur ; P. D'ADAMO, Auteur ; Elena BONORA, Auteur ; P. PARCHI, Auteur ; Raffaella TANCREDI, Auteur ; A. BATTAGLIA, Auteur ; E. 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 et/ou numérique 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 et/ou numérique] / 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

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