{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T20:02:02Z","timestamp":1788206522204,"version":"build-2803163510"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p><jats:bold>Background and Objectives:<\/jats:bold> Chromosomal microarray (CMA) is a first-tier genetic test for children with developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), and multiple congenital anomalies (MCA). In this study, we report our experiences with the use of CMA in Korean children with unexplained DD\/ID.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We performed CMA in a cohort of 308 children with DD\/ID between January 2010 and September 2020. We also retrospectively reviewed their medical records. The Affymetrix CytoScan 750 K array with an average resolution of 100 kb was used to perform CMA.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Comorbid neurodevelopmental disorders were ASD (37 patients; 12.0%), epilepsy (34 patients; 11.0%), and attention deficit hyperactivity disorders (12 patients; 3.9%). The diagnostic yield was 18.5%. Among the 221 copy number variants (CNVs) identified, 70 CNVs (57 patients; 18.5%) were pathogenic. Deletion CNVs were more common among pathogenic CNVs (PCNVs) than in non-PCNVs (<jats:italic>P<\/jats:italic> &amp;lt; 0.001). The size difference between PCNVs and non-PCNVs was not significant (<jats:italic>P<\/jats:italic> = 0.023). The number of included genes within CNV intervals was significantly higher in PCNVs (average 8.6; 0\u2013347) than in non-PCNVs (average 47.5; 1\u2013386) (<jats:italic>P<\/jats:italic> &amp;lt; 0.001). Short stature and hearing difficulty were also more common in the PCNV group than in the non-PCNV group (<jats:italic>P<\/jats:italic> = 0.010 and 0.070, respectively).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This study provides additional evidence for the usefulness of CMA in genetic testing of children with DD\/ID in Korea. The pathogenicity of CNVs correlated with the number of included genes within the CNV interval and deletion type of the CNVs, but not with CNV size.<\/jats:p>","DOI":"10.3389\/fped.2021.690493","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T13:38:01Z","timestamp":1631713081000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Chromosomal Microarray in Children With Developmental Delay: The Experience of a Tertiary Center in Korea"],"prefix":"10.3389","volume":"9","author":[{"given":"Eun Hye","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Beom","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Han","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Won","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jung","family":"Kwak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hee","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Hye","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Hyun","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Ook","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Mi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1002\/j.2051-5545.2011.tb00045.x","article-title":"Intellectual developmental disorders: towards a new name, definition and framework for \u201cmental retardation\/intellectual disability\u201d in ICD-11","volume":"10","author":"Salvador-Carulla","year":"2011","journal-title":"World Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/S0140-6736(13)61539-1","article-title":"Autism","volume":"383","author":"Lai","year":"2014","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1542\/peds.2010-2989","article-title":"Trends in the prevalence of developmental disabilities in US children, 1997\u20132008","volume":"127","author":"Boyle","year":"2011","journal-title":"Pediatrics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1212\/01.WNL.0000031431.81555.16","article-title":"Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society","volume":"60","author":"Shevell","year":"2003","journal-title":"Neurology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.ajhg.2010.04.006","article-title":"Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies","volume":"86","author":"Miller","year":"2010","journal-title":"Am J Hum Genet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"438","DOI":"10.3345\/cep.2020.00640","article-title":"Development of the Korean Developmental Screening Test for Infants and Children (K-DST)","volume":"63","author":"Chung","year":"2020","journal-title":"Clin Exp Pediatr"},{"key":"B7","volume-title":"Bayley Scales of Infant and Toddler Dvelopment","author":"Bayley","year":"2006"},{"key":"B8","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1097\/GIM.0b013e3182217a3a","article-title":"American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants","volume":"13","author":"Kearney","year":"2011","journal-title":"Genet Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e1002334","DOI":"10.1371\/journal.pgen.1002334","article-title":"Relative burden of large CNVs on a range of neurodevelopmental phenotypes","volume":"7","author":"Girirajan","year":"2011","journal-title":"PLoS Genet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1097\/GIM.0b013e31822272ac","article-title":"American College of Medical Genetics recommendations for the design and performance expectations for clinical genomic copy number microarrays intended for use in the postnatal setting for detection of constitutional abnormalities","volume":"13","author":"Kearney","year":"2011","journal-title":"Genet Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1002\/ajmg.a.32622","article-title":"Familial 14","author":"Filges","year":"2009","journal-title":"Am J Med Genet A"},{"key":"B13","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1136\/jmg.2007.055319","article-title":"Comparison of targeted and whole genome analysis of postnatal specimens using a commercially available array based comparative genomic hybridisation (aCGH) microarray platform","volume":"45","author":"Aston","year":"2008","journal-title":"J Med Genet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1002\/ajmg.a.31773","article-title":"Whole-genome array-CGH identifies novel contiguous gene deletions and duplications associated with developmental delay, mental retardation, and dysmorphic features","author":"Aradhya","year":"2007","journal-title":"Am J Med Genet A"},{"key":"B15","doi-asserted-by":"publisher","first-page":"431","DOI":"10.3349\/ymj.2018.59.3.431","article-title":"Phenotypic analysis of korean patients with abnormal chromosomal microarray in patients with unexplained developmental delay\/intellectual disability","volume":"59","author":"Kim","year":"2018","journal-title":"Yonsei Med J"},{"key":"B16","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.ajhg.2012.10.007","article-title":"Copy-number disorders are a common cause of congenital kidney malformations","volume":"91","author":"Sanna-Cherchi","year":"2012","journal-title":"Am J Hum Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41588-018-0281-y","article-title":"The copy number variation landscape of congenital anomalies of the kidney and urinary tract","volume":"51","author":"Verbitsky","year":"2019","journal-title":"Nat Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"8247","DOI":"10.3390\/ijms21218247","article-title":"Lessons learned from CNV analysis of major birth defects","volume":"21","author":"Hilger","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/j.1399-0004.2012.01850.x","article-title":"Array CGH in patients with developmental delay or intellectual disability: are there phenotypic clues to pathogenic copy number variants?","volume":"83","author":"Shoukier","year":"2013","journal-title":"Clin Genet"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.690493\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T13:38:03Z","timestamp":1631713083000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2021.690493\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,15]]},"references-count":19,"alternative-id":["10.3389\/fped.2021.690493"],"URL":"https:\/\/doi.org\/10.3389\/fped.2021.690493","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,15]]},"article-number":"690493"}}