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

Lack of replication of previous autism spectrum disorder GWAS hits in European populations / Bàrbara TORRICO in Autism Research, 10-2 (February 2017)  

Public ISBD [article]  inAutism Research > 10-2 (February 2017) . - p.202-211 Titre : Lack of replication of previous autism spectrum disorder GWAS hits in European populations Type de document : Texte imprimé et/ou numérique Auteurs : Bàrbara TORRICO, Auteur ; Andreas G. CHIOCCHETTI, Auteur ; Elena BACCHELLI, Auteur ; Elisabetta TRABETTI, Auteur ; Amaia HERVAS, Auteur ; Barbara FRANKE, Auteur ; Jan K. BUITELAAR, Auteur ; Nanda N. ROMMELSE, Auteur ; Afsheen YOUSAF, Auteur ; Eftichia DUKETIS, Auteur ; Christine M. FREITAG, Auteur ; Rafaela CABALLERO-ANDALUZ, Auteur ; Amalia MARTINEZ-MIR, Auteur ; Francisco G. SCHOLL, Auteur ; Marta RIBASES, Auteur ; ITAN, Auteur ; Agatino BATTAGLIA, Auteur ; Giovanni MALERBA, Auteur ; Richard DELORME, Auteur ; Marion BENABOU, Auteur ; Elena MAESTRINI, Auteur ; Thomas BOURGERON, Auteur ; Bru CORMAND, Auteur ; Claudio TOMA, Auteur Article en page(s) : p.202-211 Langues : Anglais (eng) Mots-clés : genome-wide association study  replication  autism spectrum disorder  European populations  MACROD2  SEMA5A  MSNP1 Index. décimale : PER Périodiques Résumé : Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several genome-wide association studies (GWAS) have enabled the detection of a few plausible risk variants. The three main studies are family-based and pointed at SEMA5A (rs10513025), MACROD2 (rs4141463) and MSNP1 (rs4307059). In our study we attempted to replicate these GWAS hits using a case-control association study in five European populations of ASD patients and gender-matched controls, all Caucasians. Results showed no association of individual variants with ASD in any of the population groups considered or in the combined European sample. We performed a meta-analysis study across five European populations for rs10513025 (1,904 ASD cases and 2,674 controls), seven European populations for rs4141463 (2,855 ASD cases and 36,177 controls) and five European populations for rs4307059 (2,347 ASD cases and 2,764 controls). The results showed an odds ratio (OR) of 1.05 (95% CI?=?0.84–1.32) for rs10513025, 1.0002 (95% CI?=?0.93–1.08) for rs4141463 and 1.01 (95% CI?=?0.92–1.1) for rs4307059, with no significant P-values (rs10513025, P?=?0.73; rs4141463, P?=?0.95; rs4307059, P?=?0.9). No association was found when we considered either only high functioning autism (HFA), genders separately or only multiplex families. Ongoing GWAS projects with larger ASD cohorts will contribute to clarify the role of common variation in the disorder and will likely identify risk variants of modest effect not detected previously. En ligne : http://dx.doi.org/10.1002/aur.1662 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303 [article] Lack of replication of previous autism spectrum disorder GWAS hits in European populations [Texte imprimé et/ou numérique] / Bàrbara TORRICO, Auteur ; Andreas G. CHIOCCHETTI, Auteur ; Elena BACCHELLI, Auteur ; Elisabetta TRABETTI, Auteur ; Amaia HERVAS, Auteur ; Barbara FRANKE, Auteur ; Jan K. BUITELAAR, Auteur ; Nanda N. ROMMELSE, Auteur ; Afsheen YOUSAF, Auteur ; Eftichia DUKETIS, Auteur ; Christine M. FREITAG, Auteur ; Rafaela CABALLERO-ANDALUZ, Auteur ; Amalia MARTINEZ-MIR, Auteur ; Francisco G. SCHOLL, Auteur ; Marta RIBASES, Auteur ; ITAN, Auteur ; Agatino BATTAGLIA, Auteur ; Giovanni MALERBA, Auteur ; Richard DELORME, Auteur ; Marion BENABOU, Auteur ; Elena MAESTRINI, Auteur ; Thomas BOURGERON, Auteur ; Bru CORMAND, Auteur ; Claudio TOMA, Auteur . - p.202-211. Langues : Anglais (eng) in Autism Research > 10-2 (February 2017) . - p.202-211 Mots-clés : genome-wide association study  replication  autism spectrum disorder  European populations  MACROD2  SEMA5A  MSNP1 Index. décimale : PER Périodiques Résumé : Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several genome-wide association studies (GWAS) have enabled the detection of a few plausible risk variants. The three main studies are family-based and pointed at SEMA5A (rs10513025), MACROD2 (rs4141463) and MSNP1 (rs4307059). In our study we attempted to replicate these GWAS hits using a case-control association study in five European populations of ASD patients and gender-matched controls, all Caucasians. Results showed no association of individual variants with ASD in any of the population groups considered or in the combined European sample. We performed a meta-analysis study across five European populations for rs10513025 (1,904 ASD cases and 2,674 controls), seven European populations for rs4141463 (2,855 ASD cases and 36,177 controls) and five European populations for rs4307059 (2,347 ASD cases and 2,764 controls). The results showed an odds ratio (OR) of 1.05 (95% CI?=?0.84–1.32) for rs10513025, 1.0002 (95% CI?=?0.93–1.08) for rs4141463 and 1.01 (95% CI?=?0.92–1.1) for rs4307059, with no significant P-values (rs10513025, P?=?0.73; rs4141463, P?=?0.95; rs4307059, P?=?0.9). No association was found when we considered either only high functioning autism (HFA), genders separately or only multiplex families. Ongoing GWAS projects with larger ASD cohorts will contribute to clarify the role of common variation in the disorder and will likely identify risk variants of modest effect not detected previously. En ligne : http://dx.doi.org/10.1002/aur.1662 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303

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