CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems / S. CHENIER in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.9 Titre : CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems Type de document : Texte imprimé et/ou numérique Auteurs : S. CHENIER, Auteur ; G. YOON, Auteur ; B. ARGIROPOULOS, Auteur ; J. LAUZON, Auteur ; R. LAFRAMBOISE, Auteur ; J. W. AHN, Auteur ; C. M. OGILVIE, Auteur ; A. C. LIONEL, Auteur ; C. R. MARSHALL, Auteur ; A. K. VAAGS, Auteur ; B. HASHEMI, Auteur ; K. BOISVERT, Auteur ; G. MATHONNET, Auteur ; F. TIHY, Auteur ; J. SO, Auteur ; Stephen SCHERER, Auteur ; E. LEMYRE, Auteur ; D. J. STAVROPOULOS, Auteur Article en page(s) : p.9 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Chd2  Developmental delay  Epilepsy  Learning disability Index. décimale : PER Périodiques Résumé : BACKGROUND: The chromodomain helicase DNA binding domain (CHD) proteins modulate gene expression via their ability to remodel chromatin structure and influence histone acetylation. Recent studies have shown that CHD2 protein plays a critical role in embryonic development, tumor suppression and survival. Like other genes encoding members of the CHD family, pathogenic mutations in the CHD2 gene are expected to be implicated in human disease. In fact, there is emerging evidence suggesting that CHD2 might contribute to a broad spectrum of neurodevelopmental disorders. Despite growing evidence, a description of the full phenotypic spectrum of this condition is lacking. METHODS: We conducted a multicentre study to identify and characterise the clinical features associated with haploinsufficiency of CHD2. Patients with deletions of this gene were identified from among broadly ascertained clinical cohorts undergoing genomic microarray analysis for developmental delay, congenital anomalies and/or autism spectrum disorder. RESULTS: Detailed clinical assessments by clinical geneticists showed recurrent clinical symptoms, including developmental delay, intellectual disability, epilepsy, behavioural problems and autism-like features without characteristic facial gestalt or brain malformations observed on magnetic resonance imaging scans. Parental analysis showed that the deletions affecting CHD2 were de novo in all four patients, and analysis of high-resolution microarray data derived from 26,826 unaffected controls showed no deletions of this gene. CONCLUSIONS: The results of this study, in addition to our review of the literature, support a causative role of CHD2 haploinsufficiency in developmental delay, intellectual disability, epilepsy and behavioural problems, with phenotypic variability between individuals. En ligne : http://dx.doi.org/10.1186/1866-1955-6-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346 [article] CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems [Texte imprimé et/ou numérique] / S. CHENIER, Auteur ; G. YOON, Auteur ; B. ARGIROPOULOS, Auteur ; J. LAUZON, Auteur ; R. LAFRAMBOISE, Auteur ; J. W. AHN, Auteur ; C. M. OGILVIE, Auteur ; A. C. LIONEL, Auteur ; C. R. MARSHALL, Auteur ; A. K. VAAGS, Auteur ; B. HASHEMI, Auteur ; K. BOISVERT, Auteur ; G. MATHONNET, Auteur ; F. TIHY, Auteur ; J. SO, Auteur ; Stephen SCHERER, Auteur ; E. LEMYRE, Auteur ; D. J. STAVROPOULOS, Auteur . - p.9. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.9 Mots-clés : Autism spectrum disorder  Chd2  Developmental delay  Epilepsy  Learning disability Index. décimale : PER Périodiques Résumé : BACKGROUND: The chromodomain helicase DNA binding domain (CHD) proteins modulate gene expression via their ability to remodel chromatin structure and influence histone acetylation. Recent studies have shown that CHD2 protein plays a critical role in embryonic development, tumor suppression and survival. Like other genes encoding members of the CHD family, pathogenic mutations in the CHD2 gene are expected to be implicated in human disease. In fact, there is emerging evidence suggesting that CHD2 might contribute to a broad spectrum of neurodevelopmental disorders. Despite growing evidence, a description of the full phenotypic spectrum of this condition is lacking. METHODS: We conducted a multicentre study to identify and characterise the clinical features associated with haploinsufficiency of CHD2. Patients with deletions of this gene were identified from among broadly ascertained clinical cohorts undergoing genomic microarray analysis for developmental delay, congenital anomalies and/or autism spectrum disorder. RESULTS: Detailed clinical assessments by clinical geneticists showed recurrent clinical symptoms, including developmental delay, intellectual disability, epilepsy, behavioural problems and autism-like features without characteristic facial gestalt or brain malformations observed on magnetic resonance imaging scans. Parental analysis showed that the deletions affecting CHD2 were de novo in all four patients, and analysis of high-resolution microarray data derived from 26,826 unaffected controls showed no deletions of this gene. CONCLUSIONS: The results of this study, in addition to our review of the literature, support a causative role of CHD2 haploinsufficiency in developmental delay, intellectual disability, epilepsy and behavioural problems, with phenotypic variability between individuals. En ligne : http://dx.doi.org/10.1186/1866-1955-6-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346

Mutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly / M. WOODBURY-SMITH in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 59p. Titre : Mutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly Type de document : Texte imprimé et/ou numérique Auteurs : M. WOODBURY-SMITH, Auteur ; E. DENEAULT, Auteur ; R. K. C. YUEN, Auteur ; S. WALKER, Auteur ; M. ZARREI, Auteur ; G. PELLECCHIA, Auteur ; J. L. HOWE, Auteur ; N. HOANG, Auteur ; M. UDDIN, Auteur ; C. R. MARSHALL, Auteur ; C. CHRYSLER, Auteur ; A. THOMPSON, Auteur ; P. SZATMARI, Auteur ; Stephen SCHERER, Auteur Article en page(s) : 59p. Langues : Anglais (eng) Mots-clés : Intellectual disability (ID)  Rab39b  RNAseq  Whole genome sequencing (WGS) Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD), a developmental disorder of early childhood onset, affects males four times more frequently than females, suggesting a role for the sex chromosomes. In this study, we describe a family with ASD in which a predicted pathogenic nonsense mutation in the X-chromosome gene RAB39B segregates with ASD phenotype. Methods: Clinical phenotyping, microarray, and whole genome sequencing (WGS) were performed on the five members of this family. Maternal and female sibling X inactivation ratio was calculated, and phase was investigated. Mutant-induced pluripotent stem cells engineered for an exon 2 nonsense mutation were generated and differentiated into cortical neurons for expression and pathway analyses. Results: Two males with an inherited RAB39B mutation both presented with macrocephaly, intellectual disability (ID), and ASD. Their female sibling with the same mutation presented with ID and a broad autism phenotype. In contrast, their transmitting mother has no neurodevelopmental diagnosis. Our investigation of phase indicated maternal preferential inactivation of the mutated allele, with no such bias observed in the female sibling. We offer the explanation that this bias in X inactivation may explain the absence of a neurocognitive phenotype in the mother. Our cellular knockout model of RAB39B revealed an impact on expression in differentiated neurons for several genes implicated in brain development and function, supported by our pathway enrichment analysis. Conclusions: Penetrance for ASD is high among males but more variable among females with RAB39B mutations. A critical role for this gene in brain development and function is demonstrated. En ligne : http://dx.doi.org/10.1186/s13229-017-0175-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331 [article] Mutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly [Texte imprimé et/ou numérique] / M. WOODBURY-SMITH, Auteur ; E. DENEAULT, Auteur ; R. K. C. YUEN, Auteur ; S. WALKER, Auteur ; M. ZARREI, Auteur ; G. PELLECCHIA, Auteur ; J. L. HOWE, Auteur ; N. HOANG, Auteur ; M. UDDIN, Auteur ; C. R. MARSHALL, Auteur ; C. CHRYSLER, Auteur ; A. THOMPSON, Auteur ; P. SZATMARI, Auteur ; Stephen SCHERER, Auteur . - 59p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 59p. Mots-clés : Intellectual disability (ID)  Rab39b  RNAseq  Whole genome sequencing (WGS) Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD), a developmental disorder of early childhood onset, affects males four times more frequently than females, suggesting a role for the sex chromosomes. In this study, we describe a family with ASD in which a predicted pathogenic nonsense mutation in the X-chromosome gene RAB39B segregates with ASD phenotype. Methods: Clinical phenotyping, microarray, and whole genome sequencing (WGS) were performed on the five members of this family. Maternal and female sibling X inactivation ratio was calculated, and phase was investigated. Mutant-induced pluripotent stem cells engineered for an exon 2 nonsense mutation were generated and differentiated into cortical neurons for expression and pathway analyses. Results: Two males with an inherited RAB39B mutation both presented with macrocephaly, intellectual disability (ID), and ASD. Their female sibling with the same mutation presented with ID and a broad autism phenotype. In contrast, their transmitting mother has no neurodevelopmental diagnosis. Our investigation of phase indicated maternal preferential inactivation of the mutated allele, with no such bias observed in the female sibling. We offer the explanation that this bias in X inactivation may explain the absence of a neurocognitive phenotype in the mother. Our cellular knockout model of RAB39B revealed an impact on expression in differentiated neurons for several genes implicated in brain development and function, supported by our pathway enrichment analysis. Conclusions: Penetrance for ASD is high among males but more variable among females with RAB39B mutations. A critical role for this gene in brain development and function is demonstrated. En ligne : http://dx.doi.org/10.1186/s13229-017-0175-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331

Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders / G. COSTAIN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 3 p. Titre : Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders Type de document : Texte imprimé et/ou numérique Auteurs : G. COSTAIN, Auteur ; S. WALKER, Auteur ; B. ARGIROPOULOS, Auteur ; D. A. BARIBEAU, Auteur ; A. S. BASSETT, Auteur ; E. BOOT, Auteur ; Koenraad DEVRIENDT, Auteur ; B. KELLAM, Auteur ; C. R. MARSHALL, Auteur ; A. PRASAD, Auteur ; M. A. SERRANO, Auteur ; D. J. STAVROPOULOS, Auteur ; H. TWEDE, Auteur ; J. R. VERMEESCH, Auteur ; J. A. S. VORSTMAN, Auteur ; Stephen SCHERER, Auteur Article en page(s) : 3 p. Langues : Anglais (eng) Mots-clés : Adhd  Autism  Copy number variation  Dmxl2  Grik5  Genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. METHODS: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. RESULTS: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. CONCLUSIONS: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. En ligne : http://dx.doi.org/10.1186/s11689-019-9263-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders [Texte imprimé et/ou numérique] / G. COSTAIN, Auteur ; S. WALKER, Auteur ; B. ARGIROPOULOS, Auteur ; D. A. BARIBEAU, Auteur ; A. S. BASSETT, Auteur ; E. BOOT, Auteur ; Koenraad DEVRIENDT, Auteur ; B. KELLAM, Auteur ; C. R. MARSHALL, Auteur ; A. PRASAD, Auteur ; M. A. SERRANO, Auteur ; D. J. STAVROPOULOS, Auteur ; H. TWEDE, Auteur ; J. R. VERMEESCH, Auteur ; J. A. S. VORSTMAN, Auteur ; Stephen SCHERER, Auteur . - 3 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 3 p. Mots-clés : Adhd  Autism  Copy number variation  Dmxl2  Grik5  Genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. METHODS: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. RESULTS: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. CONCLUSIONS: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. En ligne : http://dx.doi.org/10.1186/s11689-019-9263-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation / M. J. GAZZELLONE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.36 Titre : Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation Type de document : Texte imprimé et/ou numérique Auteurs : M. J. GAZZELLONE, Auteur ; M. ZARREI, Auteur ; C. L. BURTON, Auteur ; S. WALKER, Auteur ; M. UDDIN, Auteur ; S. M. SHAHEEN, Auteur ; J. COSTE, Auteur ; R. RAJENDRAM, Auteur ; R. J. SCHACHTER, Auteur ; M. COLASANTO, Auteur ; G. L. HANNA, Auteur ; D. R. ROSENBERG, Auteur ; N. SORENI, Auteur ; K. D. FITZGERALD, Auteur ; C. R. MARSHALL, Auteur ; J. A. BUCHANAN, Auteur ; D. MERICO, Auteur ; P. D. ARNOLD, Auteur ; Stephen SCHERER, Auteur Article en page(s) : p.36 Langues : Anglais (eng) Mots-clés : Copy number variation  Obsessive-compulsive disorder  Pediatrics  Whole-exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. METHODS: We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. RESULTS: We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 x 10(-03); FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten "CNV positive" trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. CONCLUSIONS: Our findings suggest that rare CNVs may contribute to the etiology of OCD. En ligne : http://dx.doi.org/10.1186/s11689-016-9170-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation [Texte imprimé et/ou numérique] / M. J. GAZZELLONE, Auteur ; M. ZARREI, Auteur ; C. L. BURTON, Auteur ; S. WALKER, Auteur ; M. UDDIN, Auteur ; S. M. SHAHEEN, Auteur ; J. COSTE, Auteur ; R. RAJENDRAM, Auteur ; R. J. SCHACHTER, Auteur ; M. COLASANTO, Auteur ; G. L. HANNA, Auteur ; D. R. ROSENBERG, Auteur ; N. SORENI, Auteur ; K. D. FITZGERALD, Auteur ; C. R. MARSHALL, Auteur ; J. A. BUCHANAN, Auteur ; D. MERICO, Auteur ; P. D. ARNOLD, Auteur ; Stephen SCHERER, Auteur . - p.36. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.36 Mots-clés : Copy number variation  Obsessive-compulsive disorder  Pediatrics  Whole-exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. METHODS: We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. RESULTS: We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 x 10(-03); FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten "CNV positive" trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. CONCLUSIONS: Our findings suggest that rare CNVs may contribute to the etiology of OCD. En ligne : http://dx.doi.org/10.1186/s11689-016-9170-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10 / A. S. L. MAK in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 31p. Titre : Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10 Type de document : Texte imprimé et/ou numérique Auteurs : A. S. L. MAK, Auteur ; A. T. G. CHIU, Auteur ; G. K. C. LEUNG, Auteur ; C. C. Y. MAK, Auteur ; Y. W. Y. CHU, Auteur ; G. T. K. MOK, Auteur ; W. F. TANG, Auteur ; K. Y. K. CHAN, Auteur ; M. H. Y. TANG, Auteur ; E. T. LAU YIM, Auteur ; K. W. SO, Auteur ; V. Q. TAO, Auteur ; C. W. FUNG, Auteur ; Virginia C.N. WONG, Auteur ; M. UDDIN, Auteur ; S. L. LEE, Auteur ; C. R. MARSHALL, Auteur ; Stephen SCHERER, Auteur ; A. S. Y. KAN, Auteur ; B. H. Y. CHUNG, Auteur Article en page(s) : 31p. Langues : Anglais (eng) Mots-clés : Array comparative genomic hybridization (aCGH)  Autism spectrum disorder (ASD)  Chinese  Copy number variations (CNVs)  Dpp10 Index. décimale : PER Périodiques Résumé : BACKGROUND: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. METHODS: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature. RESULTS: Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3' exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases. CONCLUSIONS: The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings. En ligne : http://dx.doi.org/10.1186/s13229-017-0136-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10 [Texte imprimé et/ou numérique] / A. S. L. MAK, Auteur ; A. T. G. CHIU, Auteur ; G. K. C. LEUNG, Auteur ; C. C. Y. MAK, Auteur ; Y. W. Y. CHU, Auteur ; G. T. K. MOK, Auteur ; W. F. TANG, Auteur ; K. Y. K. CHAN, Auteur ; M. H. Y. TANG, Auteur ; E. T. LAU YIM, Auteur ; K. W. SO, Auteur ; V. Q. TAO, Auteur ; C. W. FUNG, Auteur ; Virginia C.N. WONG, Auteur ; M. UDDIN, Auteur ; S. L. LEE, Auteur ; C. R. MARSHALL, Auteur ; Stephen SCHERER, Auteur ; A. S. Y. KAN, Auteur ; B. H. Y. CHUNG, Auteur . - 31p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 31p. Mots-clés : Array comparative genomic hybridization (aCGH)  Autism spectrum disorder (ASD)  Chinese  Copy number variations (CNVs)  Dpp10 Index. décimale : PER Périodiques Résumé : BACKGROUND: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. METHODS: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature. RESULTS: Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3' exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases. CONCLUSIONS: The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings. En ligne : http://dx.doi.org/10.1186/s13229-017-0136-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

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