{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:52:01Z","timestamp":1775868721657,"version":"3.50.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"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. Genet."],"abstract":"<jats:p>This case report and literature review documents an ultra-rare <jats:italic>de novo<\/jats:italic> copy number gain at 5q14.3q15. The patient\u2019s phenotype included hypotonia, microcephaly, global developmental delay, iris hypoplasia, atrophy, sweat dysregulation, and skeletal implications, including camptodactyly. This case presentation provides novel insights into the genotype\u2013phenotype correlation for 5q14.3q15 copy number gain, particularly highlighting the involvement of the <jats:italic>MEF2C<\/jats:italic> gene (#MIM 600662). Through comprehensive clinical and genetic evaluation, we aim to enhance the understanding of this ultra-rare genetic condition and its implications.<\/jats:p>","DOI":"10.3389\/fgene.2025.1549685","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T05:17:41Z","timestamp":1748236661000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: A neurodevelopmental disorder with global developmental delay, microcephaly, eye anomalies, sweat dysregulation, and skeletal implications due to an ultra-rare de novo 5q14.3q15 copy number gain"],"prefix":"10.3389","volume":"16","author":[{"given":"Costela Lacrimioara","family":"Serban","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Mihailescu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Miclea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristian G.","family":"Zimbru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florina","family":"Stoica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela","family":"Chirita-Emandi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1097\/MCD.0b013e328331a6d7","article-title":"De-novo duplication of 5(q13.3q21.1) in a child with vitreo-retinal dysplasia and learning disability","volume":"19","author":"Banka","year":"2010","journal-title":"Clin. Dysmorphol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6733","DOI":"10.1073\/pnas.1922370117","article-title":"Arrestin domain-containing 3 (Arrdc3) modulates insulin action and glucose metabolism in liver","volume":"117","author":"Batista","year":"2020","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1186\/s13023-022-02358-x","article-title":"The diagnostic odyssey: insights from parents of children living with an undiagnosed condition","volume":"17","author":"Bauskis","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e1192","DOI":"10.1016\/S2214-109X(24)00134-7","article-title":"Global health for rare diseases through primary care","volume":"12","author":"Baynam","year":"2024","journal-title":"Lancet Glob. Health"},{"key":"B5","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1097\/MCD.0b013e32833dc589","article-title":"Late-onset gain of skills and peculiar jugular pit in an 11-year-old girl with 5q14.3 microdeletion including MEF2C","volume":"19","author":"Berland","year":"2010","journal-title":"Clin. Dysmorphol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1212\/01.wnl.0000336339.08878.2d","article-title":"Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion","volume":"72","author":"Cardoso","year":"2009","journal-title":"Neurology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1002\/ajmg.a.37594","article-title":"Prenatal detection of 5q14.3 duplication including MEF2C and brain phenotype","volume":"170","author":"Cesaretti","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3041","DOI":"10.1016\/j.cell.2022.06.036","article-title":"A cross-disorder dosage sensitivity map of the human genome","volume":"185","author":"Collins","year":"2022","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"839","DOI":"10.3390\/brainsci10110839","article-title":"7q11.23 microduplication syndrome: clinical and neurobehavioral profiling","volume":"10","author":"Dentici","year":"2020","journal-title":"Brain Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1038\/ejhg.2009.90","article-title":"A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients","volume":"17","author":"Engels","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1136\/jmg.2007.055202","article-title":"Recurrent reciprocal deletions and duplications of 16p13.11: the deletion is a risk factor for MR\/MCA while the duplication may be a rare benign variant","volume":"46","author":"Hannes","year":"2009","journal-title":"J. Med. Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1183\/16000617.0017-2016","article-title":"Why we should care about ultra-rare disease","volume":"25","author":"Harari","year":"2016","journal-title":"Eur. Respir. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.placenta.2019.10.009","article-title":"Upregulated ARRDC3 limits trophoblast cell invasion and tube formation and is associated with preeclampsia","volume":"89","author":"Lei","year":"2020","journal-title":"Placenta"},{"key":"B15","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1136\/jmg.2009.069732","article-title":"MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and\/or cerebral malformations","volume":"47","author":"Le Meur","year":"2010","journal-title":"J. Med. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.ejmg.2013.01.011","article-title":"MEF2C deletions and mutations versus duplications: a clinical comparison","volume":"56","author":"Novara","year":"2013","journal-title":"Eur. J. Med. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1002\/ajmg.b.31071","article-title":"Severe mental retardation, seizures, and hypotonia due to deletions of MEF2C","author":"Nowakowska","year":"2010","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"B18","unstructured":"Home - OMIM\n          \n          \n          2024"},{"key":"B19","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. Off. J. Am. Coll. Med. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1002\/1873-3468.12986","article-title":"ARRDC3 suppresses colorectal cancer progression through destabilizing the oncoprotein YAP","volume":"592","author":"Shen","year":"2018","journal-title":"FEBS Lett."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1089\/ars.2021.0193","article-title":"The \u03b1-arrestin ARRDC3 is an emerging multifunctional adaptor protein in cancer","volume":"36","author":"Wedegaertner","year":"2022","journal-title":"Antioxid. Redox Signal"},{"key":"B22","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s13555-022-00885-w","article-title":"Hyperhidrosis: a central nervous dysfunction of sweat secretion","volume":"13","author":"Wohlrab","year":"2023","journal-title":"Dermatol Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"9152","DOI":"10.1074\/jbc.M510217200","article-title":"Myocyte enhancer factors 2A and 2C induce dilated cardiomyopathy in transgenic mice","volume":"281","author":"Xu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12920-019-0558-8","article-title":"Disruption of chromatin organisation causes MEF2C gene overexpression in intellectual disability: a case report","volume":"12","author":"Yauy","year":"2019","journal-title":"BMC Med. Genomics"},{"key":"B25","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1002\/humu.21253","article-title":"Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression","volume":"31","author":"Zweier","year":"2010","journal-title":"Hum. Mutat."},{"key":"B26","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1159\/000337496","article-title":"The MEF2C-related and 5q14.3q15 microdeletion syndrome","volume":"2","author":"Zweier","year":"2012","journal-title":"Mol. Syndromol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1549685\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T05:17:43Z","timestamp":1748236663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1549685\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,26]]},"references-count":26,"alternative-id":["10.3389\/fgene.2025.1549685"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2025.1549685","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,26]]},"article-number":"1549685"}}