An Exploration of Physical and Phenotypic Characteristics of Bangladeshi Children with Autism Spectrum Disorder / M. A. RAHAMAN in Journal of Autism and Developmental Disorders, 51-7 (July 2021)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 51-7 (July 2021) . - p.2392-2401 Titre : An Exploration of Physical and Phenotypic Characteristics of Bangladeshi Children with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : M. A. RAHAMAN, Auteur ; M. LOPA, Auteur ; K. M. F. UDDIN, Auteur ; M. A. BAQUI, Auteur ; S. P. KEYA, Auteur ; M. O. FARUK, Auteur ; S. SARKER, Auteur ; M. BASIRUZZAMAN, Auteur ; M. ISLAM, Auteur ; A. ALBANNA, Auteur ; N. JAHAN, Auteur ; Maka CHOWDHURY, Auteur ; N. SAHA, Auteur ; M. HUSSAIN, Auteur ; C. COLOMBI, Auteur ; D. O'RIELLY, Auteur ; M. WOODBURY-SMITH, Auteur ; M. GHAZIUDDIN, Auteur ; M. M. RAHMAN, Auteur ; M. UDDIN, Auteur Article en page(s) : p.2392-2401 Langues : Anglais (eng) Mots-clés : Adolescent  Autism Spectrum Disorder/ethnology/pathology  Bangladesh/ethnology  Body Weight  Cephalometry  Child  Child, Preschool  Female  Head/pathology  Humans  Male  Phenotype  Physical Examination  Severity of Illness Index  Sex Factors  Social Behavior  Ados-2  Autism spectrum disorder  Head circumference Index. décimale : PER Périodiques Résumé : This study explored the physical and clinical phenotype of Bangladeshi children with autism spectrum disorder (ASD). A totally of 283 children who were referred for screening and administered Module 1 of the Autism Diagnostic Observation Schedule (ADOS) were included. Overall, 209 met the ADOS algorithmic cutoff for ASD. A trend for greater weight and head circumference was observed in children with ASD versus non-ASD. Head circumference was significantly (p? En ligne : http://dx.doi.org/10.1007/s10803-020-04703-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=452 [article] An Exploration of Physical and Phenotypic Characteristics of Bangladeshi Children with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / M. A. RAHAMAN, Auteur ; M. LOPA, Auteur ; K. M. F. UDDIN, Auteur ; M. A. BAQUI, Auteur ; S. P. KEYA, Auteur ; M. O. FARUK, Auteur ; S. SARKER, Auteur ; M. BASIRUZZAMAN, Auteur ; M. ISLAM, Auteur ; A. ALBANNA, Auteur ; N. JAHAN, Auteur ; Maka CHOWDHURY, Auteur ; N. SAHA, Auteur ; M. HUSSAIN, Auteur ; C. COLOMBI, Auteur ; D. O'RIELLY, Auteur ; M. WOODBURY-SMITH, Auteur ; M. GHAZIUDDIN, Auteur ; M. M. RAHMAN, Auteur ; M. UDDIN, Auteur . - p.2392-2401. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 51-7 (July 2021) . - p.2392-2401 Mots-clés : Adolescent  Autism Spectrum Disorder/ethnology/pathology  Bangladesh/ethnology  Body Weight  Cephalometry  Child  Child, Preschool  Female  Head/pathology  Humans  Male  Phenotype  Physical Examination  Severity of Illness Index  Sex Factors  Social Behavior  Ados-2  Autism spectrum disorder  Head circumference Index. décimale : PER Périodiques Résumé : This study explored the physical and clinical phenotype of Bangladeshi children with autism spectrum disorder (ASD). A totally of 283 children who were referred for screening and administered Module 1 of the Autism Diagnostic Observation Schedule (ADOS) were included. Overall, 209 met the ADOS algorithmic cutoff for ASD. A trend for greater weight and head circumference was observed in children with ASD versus non-ASD. Head circumference was significantly (p? En ligne : http://dx.doi.org/10.1007/s10803-020-04703-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=452

Copy number variation in Han Chinese individuals with autism spectrum disorder / M. J. GAZZELLONE in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.34 Titre : Copy number variation in Han Chinese individuals with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : M. J. GAZZELLONE, Auteur ; X. ZHOU, Auteur ; A. C. LIONEL, Auteur ; M. UDDIN, Auteur ; B. THIRUVAHINDRAPURAM, Auteur ; S. LIANG, Auteur ; C. SUN, Auteur ; J. WANG, Auteur ; M. ZOU, Auteur ; K. TAMMIMIES, Auteur ; S. WALKER, Auteur ; T. SELVANAYAGAM, Auteur ; J. WEI, Auteur ; Z. WANG, Auteur ; L. WU, Auteur ; Stephen SCHERER, Auteur Article en page(s) : p.34 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Copy number variations (CNVs)  Han Chinese  Microarray diagnostic testing Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASDs) are a group of neurodevelopmental conditions with a demonstrated genetic etiology. Rare (<1% frequency) copy number variations (CNVs) account for a proportion of the genetic events involved, but the contribution of these events in non-European ASD populations has not been well studied. Here, we report on rare CNVs detected in a cohort of individuals with ASD of Han Chinese background. METHODS: DNA samples were obtained from 104 ASD probands and their parents who were recruited from Harbin, China. Samples were genotyped on the Affymetrix CytoScan HD platform. Rare CNVs were identified by comparing data with 873 technology-matched controls from Ontario and 1,235 additional population controls of Han Chinese ethnicity. RESULTS: Of the probands, 8.6% had at least 1 de novo CNV (overlapping the GIGYF2, SPRY1, 16p13.3, 16p11.2, 17p13.3-17p13.2, DMD, and NAP1L6 genes/loci). Rare inherited CNVs affected other plausible neurodevelopmental candidate genes including GRID2, LINGO2, and SLC39A12. A 24-kb duplication was also identified at YWHAE, a gene previously implicated in ASD and other developmental disorders. This duplication is observed at a similar frequency in cases and in population controls and is likely a benign Asian-specific copy number polymorphism. CONCLUSIONS: Our findings help define genomic features relevant to ASD in the Han Chinese and emphasize the importance of using ancestry-matched controls in medical genetic interpretations. En ligne : http://dx.doi.org/10.1186/1866-1955-6-34 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346 [article] Copy number variation in Han Chinese individuals with autism spectrum disorder [Texte imprimé et/ou numérique] / M. J. GAZZELLONE, Auteur ; X. ZHOU, Auteur ; A. C. LIONEL, Auteur ; M. UDDIN, Auteur ; B. THIRUVAHINDRAPURAM, Auteur ; S. LIANG, Auteur ; C. SUN, Auteur ; J. WANG, Auteur ; M. ZOU, Auteur ; K. TAMMIMIES, Auteur ; S. WALKER, Auteur ; T. SELVANAYAGAM, Auteur ; J. WEI, Auteur ; Z. WANG, Auteur ; L. WU, Auteur ; Stephen SCHERER, Auteur . - p.34. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.34 Mots-clés : Autism spectrum disorder (ASD)  Copy number variations (CNVs)  Han Chinese  Microarray diagnostic testing Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASDs) are a group of neurodevelopmental conditions with a demonstrated genetic etiology. Rare (<1% frequency) copy number variations (CNVs) account for a proportion of the genetic events involved, but the contribution of these events in non-European ASD populations has not been well studied. Here, we report on rare CNVs detected in a cohort of individuals with ASD of Han Chinese background. METHODS: DNA samples were obtained from 104 ASD probands and their parents who were recruited from Harbin, China. Samples were genotyped on the Affymetrix CytoScan HD platform. Rare CNVs were identified by comparing data with 873 technology-matched controls from Ontario and 1,235 additional population controls of Han Chinese ethnicity. RESULTS: Of the probands, 8.6% had at least 1 de novo CNV (overlapping the GIGYF2, SPRY1, 16p13.3, 16p11.2, 17p13.3-17p13.2, DMD, and NAP1L6 genes/loci). Rare inherited CNVs affected other plausible neurodevelopmental candidate genes including GRID2, LINGO2, and SLC39A12. A 24-kb duplication was also identified at YWHAE, a gene previously implicated in ASD and other developmental disorders. This duplication is observed at a similar frequency in cases and in population controls and is likely a benign Asian-specific copy number polymorphism. CONCLUSIONS: Our findings help define genomic features relevant to ASD in the Han Chinese and emphasize the importance of using ancestry-matched controls in medical genetic interpretations. En ligne : http://dx.doi.org/10.1186/1866-1955-6-34 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

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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