{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:26:33Z","timestamp":1780460793239,"version":"3.54.1"},"reference-count":22,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sotos syndrome is one of the most common overgrowth diseases and it predisposes patients to cancer, generally in childhood. The prevalence of this genetic disorder is 1:10,000\u20131:50,000, and it is characterized by wide allelic heterogeneity, with more than 100 different known mutations in the nuclear receptor-binding SET domain containing protein 1 (NSD1) gene. Most of these alterations are deletions and common micro-deletions with haploinsufficiency. Singular variants are missense mutations. The present study reports a case of a 4-year-old boy with specific clinical features of Sotos syndrome and a particular complex skin hamartoma on the right femoral side, in addition to other minor findings, such as a \u201ccaf\u00e9-au-lait\u201d spot on the right hemithorax and syndactyly of the second and third right toes. NSD1 gene analysis identified a de novo missense mutation, \u201cc.[5867T&gt;A]+[=]\u201d; \u201cp.[Leu1956Gln]+[=]\u201d, that was not previously described in the literature. This mutation was localized to the functional domain of the gene and was likely the cause of Sotos syndrome in our patient. We also compared aspects of our patient\u2019s condition with the clinical features of tuberous sclerosis (TSC), which is an autosomal neurocutaneous syndrome caused by mutations in the TSC1\/TSC2 genes. These genes control cell growth and cell survival. This disorder is characterized by hamartomas in multiple organ systems, several coetaneous abnormalities, epilepsy, and increased risk of several types of tumors.<\/jats:p>","DOI":"10.3390\/ijms19103189","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T11:07:51Z","timestamp":1539688071000},"page":"3189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expanding the Clinical Spectrum of Sotos Syndrome in a Patient with the New \u201cc.[5867T&gt;A]+[=]\u201d; \u201cp.[Leu1956Gln]+[=]\u201d NSD1 Missense Mutation and Complex Skin Hamartoma"],"prefix":"10.3390","volume":"19","author":[{"given":"Annalisa","family":"Mencarelli","sequence":"first","affiliation":[{"name":"Pediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Prontera","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, S. Maria della Misericordia Hospital, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amedea","family":"Mencarelli","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, S. Maria della Misericordia Hospital, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Rogaia","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, S. Maria della Misericordia Hospital, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Stangoni","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, S. Maria della Misericordia Hospital, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Cecconi","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics, Galliera Hospital, Mura delle Cappuccine, 14, 16128 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-2837","authenticated-orcid":false,"given":"Susanna","family":"Esposito","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1097\/MOP.0b013e3283558995","article-title":"Overgrowth syndromes","volume":"24","author":"Neylon","year":"2012","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1097\/00008480-200312000-00010","article-title":"The genetics of Sotos syndrome","volume":"15","author":"Visser","year":"2003","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_3","first-page":"109","article-title":"Sotos syndrome: A study of the diagnostic criteria and natural history","volume":"271","author":"Cole","year":"1964","journal-title":"J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0378-1119(01)00750-8","article-title":"Molecular characterization of NSD1, a human homologue of the mouse NSD1 gene","volume":"279","author":"Kurotaki","year":"2001","journal-title":"Gene"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/ng863","article-title":"Haploinsufficiency of NSD1causes Sotos syndrome","volume":"30","author":"Kurotaki","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0022-3476(10)80004-6","article-title":"Risk of malignancy in Sotos syndrome","volume":"120","author":"Hersh","year":"1992","journal-title":"J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e83","DOI":"10.1158\/1078-0432.CCR-17-0631","article-title":"Recommendations for cancer surveillance in individuals with RASopathies and other rare genetic conditions with increased cancer risk","volume":"23","author":"Villani","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_8","first-page":"486","article-title":"Cerebral gigantism associated with Wilms\u2019 tumor","volume":"138","author":"Maldonado","year":"1984","journal-title":"Am. J. Dis. Child."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/sj.ejhg.5201686","article-title":"Sotos syndrome","volume":"15","author":"Rahman","year":"2007","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_10","first-page":"333","article-title":"Mutations in the NSD1 gene in patients with Sotos syndrome associate with endocrine and paracrine alterations in the IGF system","volume":"151","author":"Hoogerbrugge","year":"2004","journal-title":"Eur. J. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1017\/S0012162206001228","article-title":"Psychosocial, cognitive, and motor functioning in patients with suspected Sotos syndrome: A comparison between patients with or without NSD1 gene alterations","volume":"48","author":"Roder","year":"2006","journal-title":"Dev. Med. Child. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1086\/432082","article-title":"Genoype-phenotype associations in Sotos syndrome: An analysis of 266 individuals with NSD1 aberrations","volume":"77","author":"Douglas","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rapaccini, V., Esposito, S., Strinati, F., Allegretti, M., Manfroi, E., Miconi, F., Pitzianti, M., Prontera, P., Principi, N., and Pasini, A. (2018). A child with a c.6923_6928dup (p.Arg2308_Met2309dup) SPTAN1 mutation associated with a severe early infantile epileptic encephalopathy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071976"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1086\/345647","article-title":"NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes","volume":"72","author":"Douglas","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/S0962-8924(01)02001-3","article-title":"Re-SET-ting heterochromatin by histone methyltransferases","volume":"11","author":"Jenuwein","year":"2001","journal-title":"Trends Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1002\/ajmg.a.38666","article-title":"Two novel cases expanding the phenotype of SETD2-related overgrowth syndrome","volume":"176","author":"Hollink","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.pediatrneurol.2008.11.013","article-title":"A clinic study of Sotos syndrome patients with review of the literature","volume":"40","author":"Leventopoulos","year":"2009","journal-title":"Pediatr. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/ajmg.c.30064","article-title":"Risk of tumorigenesis in overgrowth syndromes: A comprehensive review","volume":"137C","author":"Lapunzina","year":"2005","journal-title":"Am. J. Med. Genet. C"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2013.08.001","article-title":"Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference","volume":"49","author":"Northrup","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1093\/neuonc\/nov152","article-title":"Differentiating the mTor inhibitors everolimusand sirolimus in the treatment of tuberous sclerosis complex","volume":"17","author":"MacKeigan","year":"2015","journal-title":"Neuro Oncol."},{"key":"ref_21","first-page":"695","article-title":"Dermatological manifestations of tuberous sclerosis complex (TSC)","volume":"15","author":"Meyer","year":"2017","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1136\/jmg.40.1.51","article-title":"Familiar Sotos Syndrome is caused by a novel 1bp deletion of the NSD1 gene","volume":"40","author":"Hougland","year":"2003","journal-title":"J. Med. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/3189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:25:55Z","timestamp":1760196355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/3189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,16]]},"references-count":22,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["ijms19103189"],"URL":"https:\/\/doi.org\/10.3390\/ijms19103189","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,16]]}}}