An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males / Ren-Hua CHUNG in Molecular Autism, (November 2011)  

Public ISBD [article]  inMolecular Autism > (November 2011) . - 10 p. Titre : An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males Type de document : Texte imprimé et/ou numérique Auteurs : Ren-Hua CHUNG, Auteur ; Deqiong MA, Auteur ; Kai WANG, Auteur ; Dale HEDGES, Auteur ; James M. JAWORSKI, Auteur ; John R. GILBERT, Auteur ; Michael L. CUCCARO, Auteur ; Harry H. WRIGHT, Auteur ; Ruth K. ABRAMSON, Auteur ; Ioanna KONIDARI, Auteur ; Patrice L. WHITEHEAD, Auteur ; Gerard SCHELLENBERG, Auteur ; Hakon HAKONARSON, Auteur ; Jonathan L. HAINES, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur ; Eden R. MARTIN, Auteur Année de publication : 2011 Article en page(s) : 10 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes in people with ASD.METHODS:We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set. We performed meta- and joint analyses on the combined family and case-control data sets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family data sets as a discovery data set and the case-control data set as a validation data set.RESULTS:One SNP, rs17321050, in the transducin beta-like 1X-linked (TBL1X) gene [OMIM:300196] showed chromosome-wide significance in the meta-analysis (P value = 4.86 x 10-6) and joint analysis (P value = 4.53 x 10-6) in males. The SNP was also close to the replication threshold of 0.0025 in the discovery data set (P = 5.89 x 10-3) and passed the replication threshold in the validation data set (P = 2.56 x 10-4). Two other SNPs in the same gene in linkage disequilibrium with rs17321050 also showed significance close to the chromosome-wide threshold in the meta-analysis.CONCLUSIONS:TBL1X is in the Wnt signaling pathway, which has previously been implicated as having a role in autism. Deletions in the Xp22.2 to Xp22.3 region containing TBL1X and surrounding genes are associated with several genetic syndromes that include intellectual disability and autistic features. Our results, based on meta-analysis, joint analysis and replication analysis, suggest that TBL1X may play a role in ASD risk. En ligne : http://dx.doi.org/10.1186/2040-2392-2-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149 [article] An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males [Texte imprimé et/ou numérique] / Ren-Hua CHUNG, Auteur ; Deqiong MA, Auteur ; Kai WANG, Auteur ; Dale HEDGES, Auteur ; James M. JAWORSKI, Auteur ; John R. GILBERT, Auteur ; Michael L. CUCCARO, Auteur ; Harry H. WRIGHT, Auteur ; Ruth K. ABRAMSON, Auteur ; Ioanna KONIDARI, Auteur ; Patrice L. WHITEHEAD, Auteur ; Gerard SCHELLENBERG, Auteur ; Hakon HAKONARSON, Auteur ; Jonathan L. HAINES, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur ; Eden R. MARTIN, Auteur . - 2011 . - 10 p. Langues : Anglais (eng) in Molecular Autism > (November 2011) . - 10 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes in people with ASD.METHODS:We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set. We performed meta- and joint analyses on the combined family and case-control data sets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family data sets as a discovery data set and the case-control data set as a validation data set.RESULTS:One SNP, rs17321050, in the transducin beta-like 1X-linked (TBL1X) gene [OMIM:300196] showed chromosome-wide significance in the meta-analysis (P value = 4.86 x 10-6) and joint analysis (P value = 4.53 x 10-6) in males. The SNP was also close to the replication threshold of 0.0025 in the discovery data set (P = 5.89 x 10-3) and passed the replication threshold in the validation data set (P = 2.56 x 10-4). Two other SNPs in the same gene in linkage disequilibrium with rs17321050 also showed significance close to the chromosome-wide threshold in the meta-analysis.CONCLUSIONS:TBL1X is in the Wnt signaling pathway, which has previously been implicated as having a role in autism. Deletions in the Xp22.2 to Xp22.3 region containing TBL1X and surrounding genes are associated with several genetic syndromes that include intellectual disability and autistic features. Our results, based on meta-analysis, joint analysis and replication analysis, suggest that TBL1X may play a role in ASD risk. En ligne : http://dx.doi.org/10.1186/2040-2392-2-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149

Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci / Dale HEDGES in Molecular Autism, (April 2012)  

Public ISBD [article]  inMolecular Autism > (April 2012) . - 27 p. Titre : Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci Type de document : Texte imprimé et/ou numérique Auteurs : Dale HEDGES, Auteur ; Kara L. HAMILTON, Auteur ; Stephanie J. SACHAROW, Auteur ; Laura NATIONS, Auteur ; Gary W. BEECHAM, Auteur ; Zhanna M. KOZHEKBAEVA, Auteur ; Brittany L. BUTLER, Auteur ; Holly N. CUKIER, Auteur ; Patrice L. WHITEHEAD, Auteur ; Deqiong MA, Auteur ; James M. JAWORSKI, Auteur ; Lubov NATHANSON, Auteur ; Joycelyn M. LEE, Auteur ; Stephen L. HAUSER, Auteur ; Jorge R. OKSENBERG, Auteur ; Michael L. CUCCARO, Auteur ; Jonathan L. HAINES, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur Année de publication : 2012 Article en page(s) : 27 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders characterized by a core set of social-communicative and behavioral impairments. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors (GABR). Multiple lines of evidence, including altered GABA and GABA receptor expression in autistic patients, indicate that the GABAergic system may be involved in the etiology of autism. Methods As copy number variations (CNVs), particularly rare and de novo CNVs, have now been implicated in ASD risk, we examined the GABA receptors and genes in related pathways for structural variation that may be associated with autism. We further extended our candidate gene set to include 19 genes and regions that had either been directly implicated in the autism literature or were directly related (via function or ancestry) to these primary candidates. For the high resolution CNV screen we employed custom-designed 244 k comparative genomic hybridization (CGH) arrays. Collectively, our probes spanned a total of 11 Mb of GABA-related and additional candidate regions with a density of approximately one probe every 200 nucleotides, allowing a theoretical resolution for detection of CNVs of approximately 1 kb or greater on average. One hundred and sixty-eight autism cases and 149 control individuals were screened for structural variants. Prioritized CNV events were confirmed using quantitative PCR, and confirmed loci were evaluated on an additional set of 170 cases and 170 control individuals that were not included in the original discovery set. Loci that remained interesting were subsequently screened via quantitative PCR on an additional set of 755 cases and 1,809 unaffected family members. Results Results include rare deletions in autistic individuals at JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion polymorphisms were detected at several loci, including GABBR2 and NRXN3. Overall, statistically significant enrichment in affected vs. unaffected individuals was observed for NRXN1 deletions. En ligne : http://dx.doi.org/10.1186/2040-2392-3-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=155 [article] Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci [Texte imprimé et/ou numérique] / Dale HEDGES, Auteur ; Kara L. HAMILTON, Auteur ; Stephanie J. SACHAROW, Auteur ; Laura NATIONS, Auteur ; Gary W. BEECHAM, Auteur ; Zhanna M. KOZHEKBAEVA, Auteur ; Brittany L. BUTLER, Auteur ; Holly N. CUKIER, Auteur ; Patrice L. WHITEHEAD, Auteur ; Deqiong MA, Auteur ; James M. JAWORSKI, Auteur ; Lubov NATHANSON, Auteur ; Joycelyn M. LEE, Auteur ; Stephen L. HAUSER, Auteur ; Jorge R. OKSENBERG, Auteur ; Michael L. CUCCARO, Auteur ; Jonathan L. HAINES, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur . - 2012 . - 27 p. Langues : Anglais (eng) in Molecular Autism > (April 2012) . - 27 p. Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders characterized by a core set of social-communicative and behavioral impairments. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors (GABR). Multiple lines of evidence, including altered GABA and GABA receptor expression in autistic patients, indicate that the GABAergic system may be involved in the etiology of autism. Methods As copy number variations (CNVs), particularly rare and de novo CNVs, have now been implicated in ASD risk, we examined the GABA receptors and genes in related pathways for structural variation that may be associated with autism. We further extended our candidate gene set to include 19 genes and regions that had either been directly implicated in the autism literature or were directly related (via function or ancestry) to these primary candidates. For the high resolution CNV screen we employed custom-designed 244 k comparative genomic hybridization (CGH) arrays. Collectively, our probes spanned a total of 11 Mb of GABA-related and additional candidate regions with a density of approximately one probe every 200 nucleotides, allowing a theoretical resolution for detection of CNVs of approximately 1 kb or greater on average. One hundred and sixty-eight autism cases and 149 control individuals were screened for structural variants. Prioritized CNV events were confirmed using quantitative PCR, and confirmed loci were evaluated on an additional set of 170 cases and 170 control individuals that were not included in the original discovery set. Loci that remained interesting were subsequently screened via quantitative PCR on an additional set of 755 cases and 1,809 unaffected family members. Results Results include rare deletions in autistic individuals at JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion polymorphisms were detected at several loci, including GABBR2 and NRXN3. Overall, statistically significant enrichment in affected vs. unaffected individuals was observed for NRXN1 deletions. En ligne : http://dx.doi.org/10.1186/2040-2392-3-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=155

Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility / Holly N. CUKIER in Autism Research, 2-5 (October 2009)  

Public ISBD [article]  inAutism Research > 2-5 (October 2009) . - p.258-266 Titre : Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility Type de document : Texte imprimé et/ou numérique Auteurs : Holly N. CUKIER, Auteur ; Michael L. CUCCARO, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur ; David A. SKAAR, Auteur ; Melissa Y. RAYNER-EVANS, Auteur ; Ioanna KONIDARI, Auteur ; Patrice L. WHITEHEAD, Auteur ; James M. JAWORSKI, Auteur Année de publication : 2009 Article en page(s) : p.258-266 Langues : Anglais (eng) Mots-clés : molecular-genetics paracentric-inversion fluorescent-in-situ-hybridization-(FISH) genome-wide-association-study-(GWAS) Index. décimale : PER Périodiques Résumé : Chromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99-108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint (108-110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22-31 region and targets a candidate region for further investigation. En ligne : http://dx.doi.org/10.1002/aur.96 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=938 [article] Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility [Texte imprimé et/ou numérique] / Holly N. CUKIER, Auteur ; Michael L. CUCCARO, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur ; David A. SKAAR, Auteur ; Melissa Y. RAYNER-EVANS, Auteur ; Ioanna KONIDARI, Auteur ; Patrice L. WHITEHEAD, Auteur ; James M. JAWORSKI, Auteur . - 2009 . - p.258-266. Langues : Anglais (eng) in Autism Research > 2-5 (October 2009) . - p.258-266 Mots-clés : molecular-genetics paracentric-inversion fluorescent-in-situ-hybridization-(FISH) genome-wide-association-study-(GWAS) Index. décimale : PER Périodiques Résumé : Chromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99-108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint (108-110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22-31 region and targets a candidate region for further investigation. En ligne : http://dx.doi.org/10.1002/aur.96 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=938

A noise-reduction GWAS analysis implicates altered regulation of neurite outgrowth and guidance in autism / John P. HUSSMAN in Molecular Autism, (January 2011)  

Public ISBD [article]  inMolecular Autism > (January 2011) . - 16 p. Titre : A noise-reduction GWAS analysis implicates altered regulation of neurite outgrowth and guidance in autism Type de document : Texte imprimé et/ou numérique Auteurs : John P. HUSSMAN, Auteur ; Ren-Hua CHUNG, Auteur ; Anthony J. GRISWOLD, Auteur ; James M. JAWORSKI, Auteur ; Daria SALYAKINA, Auteur ; Deqiong MA, Auteur ; Ioanna KONIDARI, Auteur ; Patrice L. WHITEHEAD, Auteur ; Jeffery M. VANCE, Auteur ; Eden R. MARTIN, Auteur ; Michael L. CUCCARO, Auteur ; John R. GILBERT, Auteur ; Jonathan L. HAINES, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur Année de publication : 2011 Article en page(s) : 16 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Genome-wide Association Studies (GWAS) have proved invaluable for the identification of disease susceptibility genes. However, the prioritization of candidate genes and regions for follow-up studies often proves difficult due to false-positive associations caused by statistical noise and multiple-testing. In order to address this issue, we propose the novel GWAS noise reduction (GWAS-NR) method as a way to increase the power to detect true associations in GWAS, particularly in complex diseases such as autism. Methods GWAS-NR utilizes a linear filter to identify genomic regions demonstrating correlation among association signals in multiple datasets. We used computer simulations to assess the ability of GWAS-NR to detect association against the commonly used joint analysis and Fisher's methods. Furthermore, we applied GWAS-NR to a family-based autism GWAS of 597 families and a second existing autism GWAS of 696 families from the Autism Genetic Resource Exchange (AGRE) to arrive at a compendium of autism candidate genes. These genes were manually annotated and classified by a literature review and functional grouping in order to reveal biological pathways which might contribute to autism aetiology. Results Computer simulations indicate that GWAS-NR achieves a significantly higher classification rate for true positive association signals than either the joint analysis or Fisher's methods and that it can also achieve this when there is imperfect marker overlap across datasets or when the closest disease-related polymorphism is not directly typed. In two autism datasets, GWAS-NR analysis resulted in 1535 significant linkage disequilibrium (LD) blocks overlapping 431 unique reference sequencing (RefSeq) genes. Moreover, we identified the nearest RefSeq gene to the non-gene overlapping LD blocks, producing a final candidate set of 860 genes. Functional categorization of these implicated genes indicates that a significant proportion of them cooperate in a coherent pathway that regulates the directional protrusion of axons and dendrites to their appropriate synaptic targets. Conclusions As statistical noise is likely to particularly affect studies of complex disorders, where genetic heterogeneity or interaction between genes may confound the ability to detect association, GWAS-NR offers a powerful method for prioritizing regions for follow-up studies. Applying this method to autism datasets, GWAS-NR analysis indicates that a large subset of genes involved in the outgrowth and guidance of axons and dendrites is implicated in the aetiology of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121 [article] A noise-reduction GWAS analysis implicates altered regulation of neurite outgrowth and guidance in autism [Texte imprimé et/ou numérique] / John P. HUSSMAN, Auteur ; Ren-Hua CHUNG, Auteur ; Anthony J. GRISWOLD, Auteur ; James M. JAWORSKI, Auteur ; Daria SALYAKINA, Auteur ; Deqiong MA, Auteur ; Ioanna KONIDARI, Auteur ; Patrice L. WHITEHEAD, Auteur ; Jeffery M. VANCE, Auteur ; Eden R. MARTIN, Auteur ; Michael L. CUCCARO, Auteur ; John R. GILBERT, Auteur ; Jonathan L. HAINES, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur . - 2011 . - 16 p. Langues : Anglais (eng) in Molecular Autism > (January 2011) . - 16 p. Index. décimale : PER Périodiques Résumé : Background Genome-wide Association Studies (GWAS) have proved invaluable for the identification of disease susceptibility genes. However, the prioritization of candidate genes and regions for follow-up studies often proves difficult due to false-positive associations caused by statistical noise and multiple-testing. In order to address this issue, we propose the novel GWAS noise reduction (GWAS-NR) method as a way to increase the power to detect true associations in GWAS, particularly in complex diseases such as autism. Methods GWAS-NR utilizes a linear filter to identify genomic regions demonstrating correlation among association signals in multiple datasets. We used computer simulations to assess the ability of GWAS-NR to detect association against the commonly used joint analysis and Fisher's methods. Furthermore, we applied GWAS-NR to a family-based autism GWAS of 597 families and a second existing autism GWAS of 696 families from the Autism Genetic Resource Exchange (AGRE) to arrive at a compendium of autism candidate genes. These genes were manually annotated and classified by a literature review and functional grouping in order to reveal biological pathways which might contribute to autism aetiology. Results Computer simulations indicate that GWAS-NR achieves a significantly higher classification rate for true positive association signals than either the joint analysis or Fisher's methods and that it can also achieve this when there is imperfect marker overlap across datasets or when the closest disease-related polymorphism is not directly typed. In two autism datasets, GWAS-NR analysis resulted in 1535 significant linkage disequilibrium (LD) blocks overlapping 431 unique reference sequencing (RefSeq) genes. Moreover, we identified the nearest RefSeq gene to the non-gene overlapping LD blocks, producing a final candidate set of 860 genes. Functional categorization of these implicated genes indicates that a significant proportion of them cooperate in a coherent pathway that regulates the directional protrusion of axons and dendrites to their appropriate synaptic targets. Conclusions As statistical noise is likely to particularly affect studies of complex disorders, where genetic heterogeneity or interaction between genes may confound the ability to detect association, GWAS-NR offers a powerful method for prioritizing regions for follow-up studies. Applying this method to autism datasets, GWAS-NR analysis indicates that a large subset of genes involved in the outgrowth and guidance of axons and dendrites is implicated in the aetiology of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121

A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis / Anthony J. GRISWOLD in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.221-227 Titre : A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis Type de document : Texte imprimé et/ou numérique Auteurs : Anthony J. GRISWOLD, Auteur ; Deqiong MA, Auteur ; Stephanie J. SACHAROW, Auteur ; Joycelyn L. ROBINSON, Auteur ; James M. JAWORSKI, Auteur ; Harry H. WRIGHT, Auteur ; Ruth K. ABRAMSON, Auteur ; Helle LYBAEK, Auteur ; Nina OYEN, Auteur ; Michael L. CUCCARO, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur Année de publication : 2011 Article en page(s) : p.221-227 Langues : Anglais (eng) Mots-clés : genetics  copy number variation  molecular genetics Index. décimale : PER Périodiques Résumé : Autism is a neuro-developmental disorder characterized by deficits in social interaction and communication as well as restricted interests or repetitive behaviors. Cytogenetic studies have implicated large chromosomal aberrations in the etiology of approximately 5–7% of autism patients, and the recent advent of array-based techniques allows the exploration of submicroscopic copy number variations (CNVs). We genotyped a 14-year-old boy with autism, spherocytosis and other physical dysmorphia, his parents, and two non-autistic siblings with the Illumina Human 1M Beadchip as part of a study of the molecular genetics of autism and determined copy number variants using the PennCNV algorithm. We identified and validated a de novo 1.5 Mb microdeletion of 14q23.2-23.3 in our autistic patient. This region contains 15 genes, including spectrin beta (SPTB), encoding a cytoskeletal protein previously associated with spherocytosis, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a folate metabolizing enzyme previously associated with bipoloar disorder and schizophrenia, pleckstrin homology domain-containing family G member 3 (PLEKHG3), a guanide nucleotide exchange enriched in the brain, and churchill domain containing protein 1 (CHURC1), homologs of which regulate neuronal development in model organisms. While a similar deletion has previously been reported in a family with spherocytosis, severe learning disabilities, and mild mental retardation, this is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk. En ligne : http://dx.doi.org/10.1002/aur.186 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis [Texte imprimé et/ou numérique] / Anthony J. GRISWOLD, Auteur ; Deqiong MA, Auteur ; Stephanie J. SACHAROW, Auteur ; Joycelyn L. ROBINSON, Auteur ; James M. JAWORSKI, Auteur ; Harry H. WRIGHT, Auteur ; Ruth K. ABRAMSON, Auteur ; Helle LYBAEK, Auteur ; Nina OYEN, Auteur ; Michael L. CUCCARO, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur . - 2011 . - p.221-227. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.221-227 Mots-clés : genetics  copy number variation  molecular genetics Index. décimale : PER Périodiques Résumé : Autism is a neuro-developmental disorder characterized by deficits in social interaction and communication as well as restricted interests or repetitive behaviors. Cytogenetic studies have implicated large chromosomal aberrations in the etiology of approximately 5–7% of autism patients, and the recent advent of array-based techniques allows the exploration of submicroscopic copy number variations (CNVs). We genotyped a 14-year-old boy with autism, spherocytosis and other physical dysmorphia, his parents, and two non-autistic siblings with the Illumina Human 1M Beadchip as part of a study of the molecular genetics of autism and determined copy number variants using the PennCNV algorithm. We identified and validated a de novo 1.5 Mb microdeletion of 14q23.2-23.3 in our autistic patient. This region contains 15 genes, including spectrin beta (SPTB), encoding a cytoskeletal protein previously associated with spherocytosis, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a folate metabolizing enzyme previously associated with bipoloar disorder and schizophrenia, pleckstrin homology domain-containing family G member 3 (PLEKHG3), a guanide nucleotide exchange enriched in the brain, and churchill domain containing protein 1 (CHURC1), homologs of which regulate neuronal development in model organisms. While a similar deletion has previously been reported in a family with spherocytosis, severe learning disabilities, and mild mental retardation, this is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk. En ligne : http://dx.doi.org/10.1002/aur.186 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

Targeted massively parallel sequencing of autism spectrum disorder-associated genes in a case control cohort reveals rare loss-of-function risk variants / Anthony J. GRISWOLD in Molecular Autism, (July 2015)  

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Variants in several genomic regions associated with asperger disorder / Daria SALYAKINA in Autism Research, 3-6 (December 2010)  

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