8 recherche sur le mot-clé 'Copy number variants'

Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families / Sonja LABIANCA in Journal of Autism and Developmental Disorders, 51-1 (January 2021)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 51-1 (January 2021) . - p.276-285 Titre : Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families Type de document : Texte imprimé et/ou numérique Auteurs : Sonja LABIANCA, Auteur ; Jette LABIANCA, Auteur ; Anne Katrine PAGSBERG, Auteur ; Klaus Damgaard JAKOBSEN, Auteur ; Vivek APPADURAI, Auteur ; Alfonso BUIL, Auteur ; Thomas WERGE, Auteur Article en page(s) : p.276-285 Langues : Anglais (eng) Mots-clés : Attention deficit/hyperactivity disorder  Autism spectrum disorder  Comorbidity  Copy number variants  Families  Polygenic risk score Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly heritable neurodevelopmental disorders that frequently co-occur. Both rare and common genetic variants are important for ASD and ADHD risk but their combined contribution to clinical heterogeneity is unclear. In a sample of 39 ASD and/or ADHD families we estimated the overall variance explained by known rare copy number variants (CNVs) and polygenic risk score (PRS) from common variants to be 10% in comorbid ASD/ADHD, 4% in ASD and 2% in ADHD. We show that burden of large, rare CNVs and PRS is significantly higher in adult ASD and/or ADHD patients with sustained need for specialist care compared to their unaffected relatives, while affected relatives fall in-between the two. En ligne : http://dx.doi.org/10.1007/s10803-020-04552-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=437 [article] Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families [Texte imprimé et/ou numérique] / Sonja LABIANCA, Auteur ; Jette LABIANCA, Auteur ; Anne Katrine PAGSBERG, Auteur ; Klaus Damgaard JAKOBSEN, Auteur ; Vivek APPADURAI, Auteur ; Alfonso BUIL, Auteur ; Thomas WERGE, Auteur . - p.276-285. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 51-1 (January 2021) . - p.276-285 Mots-clés : Attention deficit/hyperactivity disorder  Autism spectrum disorder  Comorbidity  Copy number variants  Families  Polygenic risk score Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly heritable neurodevelopmental disorders that frequently co-occur. Both rare and common genetic variants are important for ASD and ADHD risk but their combined contribution to clinical heterogeneity is unclear. In a sample of 39 ASD and/or ADHD families we estimated the overall variance explained by known rare copy number variants (CNVs) and polygenic risk score (PRS) from common variants to be 10% in comorbid ASD/ADHD, 4% in ASD and 2% in ADHD. We show that burden of large, rare CNVs and PRS is significantly higher in adult ASD and/or ADHD patients with sustained need for specialist care compared to their unaffected relatives, while affected relatives fall in-between the two. En ligne : http://dx.doi.org/10.1007/s10803-020-04552-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=437

Investigating the effects of copy number variants on reading and language performance / A. GIALLUISI in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.17 Titre : Investigating the effects of copy number variants on reading and language performance Type de document : Texte imprimé et/ou numérique Auteurs : A. GIALLUISI, Auteur ; A. VISCONTI, Auteur ; E. G. WILLCUTT, Auteur ; S. D. SMITH, Auteur ; B. F. PENNINGTON, Auteur ; M. FALCHI, Auteur ; J. C. DEFRIES, Auteur ; R. K. OLSON, Auteur ; C. FRANCKS, Auteur ; S. E. FISHER, Auteur Article en page(s) : p.17 Langues : Anglais (eng) Mots-clés : Cldrc  Copy number variants  Developmental dyslexia  Family-based GWAS  Language  Meta-analysis  Reading  Reading disability Index. décimale : PER Périodiques Résumé : BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV-), and we analyzed continuous probe intensity data using FamCNV. RESULTS: No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10(-2)-10(-3)) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026-0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand-gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10(-2)-10(-4)) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls. CONCLUSIONS: These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language. En ligne : http://dx.doi.org/10.1186/s11689-016-9147-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Investigating the effects of copy number variants on reading and language performance [Texte imprimé et/ou numérique] / A. GIALLUISI, Auteur ; A. VISCONTI, Auteur ; E. G. WILLCUTT, Auteur ; S. D. SMITH, Auteur ; B. F. PENNINGTON, Auteur ; M. FALCHI, Auteur ; J. C. DEFRIES, Auteur ; R. K. OLSON, Auteur ; C. FRANCKS, Auteur ; S. E. FISHER, Auteur . - p.17. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.17 Mots-clés : Cldrc  Copy number variants  Developmental dyslexia  Family-based GWAS  Language  Meta-analysis  Reading  Reading disability Index. décimale : PER Périodiques Résumé : BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV-), and we analyzed continuous probe intensity data using FamCNV. RESULTS: No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10(-2)-10(-3)) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026-0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand-gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10(-2)-10(-4)) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls. CONCLUSIONS: These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language. En ligne : http://dx.doi.org/10.1186/s11689-016-9147-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Early developmental concerns in 22q11.2 deletion and duplication carriers / Eve S. KORTANEK in Research in Autism Spectrum Disorders, 97 (September 2022)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 97 (September 2022) . - 102026 Titre : Early developmental concerns in 22q11.2 deletion and duplication carriers Type de document : Texte imprimé et/ou numérique Auteurs : Eve S. KORTANEK, Auteur ; Nicole M. MCDONALD, Auteur ; Erin E. NOSCO, Auteur ; Gabrielle A. MACNAUGHTON, Auteur ; Amy LIN, Auteur ; Shafali S. JESTE, Auteur ; Carrie E. BEARDEN, Auteur Article en page(s) : 102026 Langues : Anglais (eng) Mots-clés : Copy number variants  22q11.2  Early development  Developmental concerns  Social communication Index. décimale : PER Périodiques Résumé : Background 22q11.2 deletions (22qDEL) and duplications (22qDUP) are among the most common copy number variants (CNVs) associated with neurodevelopmental disorders (NDDs). Little is known about the earliest developmental features of 22q11.2 CNVs and whether developmental delays are detected in early childhood. This study primarily aimed to assess general development and social communication in 22q11.2 CNV carriers age 5 and under. Method Participants included parents of children age 5 and under with a reported genetic diagnosis of 22qDEL (N = 63) or 22qDUP (N = 30). In addition to questions addressing clinical and intervention information, two standardized parent questionnaires ”the Ages & Stages Questionnaires, Third Edition (ASQ-3) and the Communication and Symbolic Behavior Scales Developmental Profile Infant/Toddler Checklist (ITC) ”screened for developmental and social communication delays, respectively. Results Developmental delay and speech and/or language delay were the most commonly reported NDD diagnoses among young 22q11.2 CNV carriers, with prevalences at 19% and 17%, respectively. In the vast majority (91%) of 22q11.2 CNV carriers, parents reported concerns in at least one developmental domain, with 71% reporting global developmental concerns. 70% of parents of 22q11.2 CNV carriers age 2 and under also reported social communication concerns. Conclusions The high prevalence of reported developmental concerns in both CNV groups reinforces the need for close monitoring of early neurodevelopment in 22q11.2 CNV carriers with regard to both developmental delays and autism risk. En ligne : https://doi.org/10.1016/j.rasd.2022.102026 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486 [article] Early developmental concerns in 22q11.2 deletion and duplication carriers [Texte imprimé et/ou numérique] / Eve S. KORTANEK, Auteur ; Nicole M. MCDONALD, Auteur ; Erin E. NOSCO, Auteur ; Gabrielle A. MACNAUGHTON, Auteur ; Amy LIN, Auteur ; Shafali S. JESTE, Auteur ; Carrie E. BEARDEN, Auteur . - 102026. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 97 (September 2022) . - 102026 Mots-clés : Copy number variants  22q11.2  Early development  Developmental concerns  Social communication Index. décimale : PER Périodiques Résumé : Background 22q11.2 deletions (22qDEL) and duplications (22qDUP) are among the most common copy number variants (CNVs) associated with neurodevelopmental disorders (NDDs). Little is known about the earliest developmental features of 22q11.2 CNVs and whether developmental delays are detected in early childhood. This study primarily aimed to assess general development and social communication in 22q11.2 CNV carriers age 5 and under. Method Participants included parents of children age 5 and under with a reported genetic diagnosis of 22qDEL (N = 63) or 22qDUP (N = 30). In addition to questions addressing clinical and intervention information, two standardized parent questionnaires ”the Ages & Stages Questionnaires, Third Edition (ASQ-3) and the Communication and Symbolic Behavior Scales Developmental Profile Infant/Toddler Checklist (ITC) ”screened for developmental and social communication delays, respectively. Results Developmental delay and speech and/or language delay were the most commonly reported NDD diagnoses among young 22q11.2 CNV carriers, with prevalences at 19% and 17%, respectively. In the vast majority (91%) of 22q11.2 CNV carriers, parents reported concerns in at least one developmental domain, with 71% reporting global developmental concerns. 70% of parents of 22q11.2 CNV carriers age 2 and under also reported social communication concerns. Conclusions The high prevalence of reported developmental concerns in both CNV groups reinforces the need for close monitoring of early neurodevelopment in 22q11.2 CNV carriers with regard to both developmental delays and autism risk. En ligne : https://doi.org/10.1016/j.rasd.2022.102026 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486

SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder / Sören MERKER in Journal of Child Psychology and Psychiatry, 58-7 (July 2017)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 58-7 (July 2017) . - p.798-809 Titre : SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder Type de document : Texte imprimé et/ou numérique Auteurs : Sören MERKER, Auteur ; Andreas REIF, Auteur ; Georg C. ZIEGLER, Auteur ; Heike WEBER, Auteur ; Ute MAYER, Auteur ; Ann-Christine EHLIS, Auteur ; Annette CONZELMANN, Auteur ; Stefan JOHANSSON, Auteur ; Clemens MÜLLER-REIBLE, Auteur ; Indrajit NANDA, Auteur ; Thomas HAAF, Auteur ; Reinhard ULLMANN, Auteur ; Marcel ROMANOS, Auteur ; Andreas J. FALLGATTER, Auteur ; Paul PAULI, Auteur ; Tatyana STREKALOVA, Auteur ; Charline JANSCH, Auteur ; Alejandro ARIAS-VASQUEZ, Auteur ; Jan HAAVIK, Auteur ; Marta RIBASES, Auteur ; Josep Antoni RAMOS-QUIROGA, Auteur ; Jan K. BUITELAAR, Auteur ; Barbara FRANKE, Auteur ; Klaus-Peter LESCH, Auteur Article en page(s) : p.798-809 Langues : Anglais (eng) Mots-clés : Attention-deficit/hyperactivity disorder  glucose transporter  SLC2A3  single-nucleotide polymorphisms  duplication  copy number variants  energy homeostasis  frontostriatal network Index. décimale : PER Périodiques Résumé : Background Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory–inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Methods Case–control association analyses of SLC2A3 single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Results Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Conclusions Taken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk. En ligne : http://dx.doi.org/10.1111/jcpp.12702 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=316 [article] SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder [Texte imprimé et/ou numérique] / Sören MERKER, Auteur ; Andreas REIF, Auteur ; Georg C. ZIEGLER, Auteur ; Heike WEBER, Auteur ; Ute MAYER, Auteur ; Ann-Christine EHLIS, Auteur ; Annette CONZELMANN, Auteur ; Stefan JOHANSSON, Auteur ; Clemens MÜLLER-REIBLE, Auteur ; Indrajit NANDA, Auteur ; Thomas HAAF, Auteur ; Reinhard ULLMANN, Auteur ; Marcel ROMANOS, Auteur ; Andreas J. FALLGATTER, Auteur ; Paul PAULI, Auteur ; Tatyana STREKALOVA, Auteur ; Charline JANSCH, Auteur ; Alejandro ARIAS-VASQUEZ, Auteur ; Jan HAAVIK, Auteur ; Marta RIBASES, Auteur ; Josep Antoni RAMOS-QUIROGA, Auteur ; Jan K. BUITELAAR, Auteur ; Barbara FRANKE, Auteur ; Klaus-Peter LESCH, Auteur . - p.798-809. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 58-7 (July 2017) . - p.798-809 Mots-clés : Attention-deficit/hyperactivity disorder  glucose transporter  SLC2A3  single-nucleotide polymorphisms  duplication  copy number variants  energy homeostasis  frontostriatal network Index. décimale : PER Périodiques Résumé : Background Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory–inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Methods Case–control association analyses of SLC2A3 single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Results Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Conclusions Taken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk. En ligne : http://dx.doi.org/10.1111/jcpp.12702 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=316

In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? / Z. MOTAHARI in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 7 p. Titre : In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? Type de document : Texte imprimé et/ou numérique Auteurs : Z. MOTAHARI, Auteur ; S. A. MOODY, Auteur ; T. M. MAYNARD, Auteur ; A. S. LAMANTIA, Auteur Article en page(s) : 7 p. Langues : Anglais (eng) Mots-clés : 22q11DS  Cardiovascular  Cognition  Copy number variants  Craniofacial  Neural development  Polygenic Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS), a copy number variation (CNV) disorder, occurs in approximately 1:4000 live births due to a heterozygous microdeletion at position 11.2 (proximal) on the q arm of human chromosome 22 (hChr22) (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011). This disorder was known as DiGeorge syndrome, Velo-cardio-facial syndrome (VCFS) or conotruncal anomaly face syndrome (CTAF) based upon diagnostic cardiovascular, pharyngeal, and craniofacial anomalies (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011; Burn et al., J Med Genet 30:822-4, 1993) before this phenotypic spectrum was associated with 22q11.2 CNVs. Subsequently, 22q11.2 deletion emerged as a major genomic lesion associated with vulnerability for several clinically defined behavioral deficits common to a number of neurodevelopmental disorders (Fernandez et al., Principles of Developmental Genetics, 2015; Robin and Shprintzen, J Pediatr 147:90-6, 2005; Schneider et al., Am J Psychiatry 171:627-39, 2014). RESULTS: The mechanistic relationships between heterozygously deleted 22q11.2 genes and 22q11DS phenotypes are still unknown. We assembled a comprehensive "line-up" of the 36 protein coding loci in the 1.5 Mb minimal critical deleted region on hChr22q11.2, plus 20 protein coding loci in the distal 1.5 Mb that defines the 3 Mb typical 22q11DS deletion. We categorized candidates based upon apparent primary cell biological functions. We analyzed 41 of these genes that encode known proteins to determine whether haploinsufficiency of any single 22q11.2 gene-a one gene to one phenotype correspondence due to heterozygous deletion restricted to that locus-versus complex multigenic interactions can account for single or multiple 22q11DS phenotypes. CONCLUSIONS: Our 22q11.2 functional genomic assessment does not support current theories of single gene haploinsufficiency for one or all 22q11DS phenotypes. Shared molecular functions, convergence on fundamental cell biological processes, and related consequences of individual 22q11.2 genes point to a matrix of multigenic interactions due to diminished 22q11.2 gene dosage. These interactions target fundamental cellular mechanisms essential for development, maturation, or homeostasis at subsets of 22q11DS phenotypic sites. En ligne : https://dx.doi.org/10.1186/s11689-019-9267-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? [Texte imprimé et/ou numérique] / Z. MOTAHARI, Auteur ; S. A. MOODY, Auteur ; T. M. MAYNARD, Auteur ; A. S. LAMANTIA, Auteur . - 7 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 7 p. Mots-clés : 22q11DS  Cardiovascular  Cognition  Copy number variants  Craniofacial  Neural development  Polygenic Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS), a copy number variation (CNV) disorder, occurs in approximately 1:4000 live births due to a heterozygous microdeletion at position 11.2 (proximal) on the q arm of human chromosome 22 (hChr22) (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011). This disorder was known as DiGeorge syndrome, Velo-cardio-facial syndrome (VCFS) or conotruncal anomaly face syndrome (CTAF) based upon diagnostic cardiovascular, pharyngeal, and craniofacial anomalies (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011; Burn et al., J Med Genet 30:822-4, 1993) before this phenotypic spectrum was associated with 22q11.2 CNVs. Subsequently, 22q11.2 deletion emerged as a major genomic lesion associated with vulnerability for several clinically defined behavioral deficits common to a number of neurodevelopmental disorders (Fernandez et al., Principles of Developmental Genetics, 2015; Robin and Shprintzen, J Pediatr 147:90-6, 2005; Schneider et al., Am J Psychiatry 171:627-39, 2014). RESULTS: The mechanistic relationships between heterozygously deleted 22q11.2 genes and 22q11DS phenotypes are still unknown. We assembled a comprehensive "line-up" of the 36 protein coding loci in the 1.5 Mb minimal critical deleted region on hChr22q11.2, plus 20 protein coding loci in the distal 1.5 Mb that defines the 3 Mb typical 22q11DS deletion. We categorized candidates based upon apparent primary cell biological functions. We analyzed 41 of these genes that encode known proteins to determine whether haploinsufficiency of any single 22q11.2 gene-a one gene to one phenotype correspondence due to heterozygous deletion restricted to that locus-versus complex multigenic interactions can account for single or multiple 22q11DS phenotypes. CONCLUSIONS: Our 22q11.2 functional genomic assessment does not support current theories of single gene haploinsufficiency for one or all 22q11DS phenotypes. Shared molecular functions, convergence on fundamental cell biological processes, and related consequences of individual 22q11.2 genes point to a matrix of multigenic interactions due to diminished 22q11.2 gene dosage. These interactions target fundamental cellular mechanisms essential for development, maturation, or homeostasis at subsets of 22q11DS phenotypic sites. En ligne : https://dx.doi.org/10.1186/s11689-019-9267-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Autism spectrum disorder symptom expression in individuals with 3q29 deletion syndrome / Rebecca M. POLLAK in Molecular Autism, 13 (2022)  

Permalink

Germ-cell-specific transcriptome analysis illuminates the chromatin and ubiquitin pathway in autism spectrum disorders / Sawako Furukawa in Autism Research, 16-6 (June 2023)  

Permalink

Neuropsychiatric phenotypes and a distinct constellation of ASD features in 3q29 deletion syndrome: results from the 3q29 registry / R. M. POLLAK in Molecular Autism, 10 (2019)  

Permalink