{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T02:08:24Z","timestamp":1784081304703,"version":"3.55.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Next generation sequencing (NGS) has expanded the diagnostic paradigm turning the focus to the growth plate. The aim of the study was to determine the prevalence of variants in genes implicated in skeletal dysplasias in probands with short stature and mild skeletal anomalies.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>Clinical and radiological data were collected from 108 probands with short stature and mild skeletal anomalies.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>A customized skeletal dysplasia NGS panel was performed. Variants were classified using ACMG recommendations and Sherloc. Anthropometric measurements and skeletal anomalies were subsequently compared in those with or without an identified genetic defect.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Heterozygous variants were identified in 21\/108 probands (19.4%). Variants were most frequently identified in <jats:italic>ACAN<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009= 10) and <jats:italic>IHH<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009= 7) whilst one variant was detected in <jats:italic>COL2A1<\/jats:italic>, <jats:italic>CREBBP<\/jats:italic>, <jats:italic>EXT1<\/jats:italic>, and <jats:italic>PTPN11<\/jats:italic>. Statistically significant differences (<jats:italic>P<\/jats:italic>\u2009&lt; 0.05) were observed for sitting height\/height (SH\/H) ratio, SH\/H ratio standard deviation score (SDS), and the SH\/H ratio SDS &gt;1 in those with an identified variant compared to those without.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>A molecular defect was elucidated in a fifth of patients. Thus, the prevalence of mild forms of skeletal dysplasias is relatively high in individuals with short stature and mild skeletal anomalies, with variants in <jats:italic>ACAN<\/jats:italic> and <jats:italic>IHH<\/jats:italic> accounting for 81% of the cases. An elevated SH\/H ratio appears to be associated with a greater probability in detecting a variant, but no other clinical or radiological feature has been found determinant to finding a genetic cause. Currently, we cannot perform extensive molecular studies in all short stature individuals so detailed clinical and radiological phenotyping may orientate which are the candidate patients to obtain worthwhile results. In addition, detailed phenotyping of probands and family members will often aid variant classification.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0557","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T17:59:28Z","timestamp":1631555968000},"page":"691-705","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":23,"title":["High prevalence of variants in skeletal dysplasia associated genes in individuals with short stature and minor skeletal anomalies"],"prefix":"10.1093","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4083-3352","authenticated-orcid":true,"given":"Luc\u00eda","family":"Sentchordi-Montan\u00e9","sequence":"first","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"2Department of Pediatrics, Hospital Universitario Infanta Leonor, Madrid, Spain"},{"name":"3Department of Pediatrics, School of Medicine, Complutense University of Madrid, Madrid, Spain"},{"name":"4Skeletal Dysplasia Multidisciplinary Unit (UMDE) and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6101-9413","authenticated-orcid":true,"given":"Sara","family":"Benito-Sanz","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"5CIBERER, ISCIII, Madrid, Spain"},{"name":"6ERN-ITHACA, Hospital Universitario, Hospital La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Aza-Carmona","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"4Skeletal Dysplasia Multidisciplinary Unit (UMDE) and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain"},{"name":"5CIBERER, ISCIII, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1364-7586","authenticated-orcid":true,"given":"Francisca","family":"D\u00edaz-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"4Skeletal Dysplasia Multidisciplinary Unit (UMDE) and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2409-4422","authenticated-orcid":true,"given":"Silvia","family":"Modamio-H\u00f8ybj\u00f8r","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"4Skeletal Dysplasia Multidisciplinary Unit (UMDE) and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"de la Torre","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"4Skeletal Dysplasia Multidisciplinary Unit (UMDE) and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli\u00e1n","family":"Nevado","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"5CIBERER, ISCIII, Madrid, Spain"},{"name":"6ERN-ITHACA, Hospital Universitario, Hospital La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Ruiz-Oca\u00f1a","sequence":"additional","affiliation":[{"name":"7Department of Pediatrics, Hospital Universitario Puerta del Mar, C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Bezanilla-L\u00f3pez","sequence":"additional","affiliation":[{"name":"8Department of Pediatrics, Hospital Universitario Fundaci\u00f3n Alcorc\u00f3n, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Prieto","sequence":"additional","affiliation":[{"name":"9Department of Pediatrics, Hospital Universitario Cl\u00ednico Salamanca and Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Bah\u00edllo-Curieses","sequence":"additional","affiliation":[{"name":"10Department of Pediatrics, Hospital Cl\u00ednico Universitario de Valladolid, Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atilano","family":"Carcavilla","sequence":"additional","affiliation":[{"name":"4Skeletal Dysplasia Multidisciplinary Unit (UMDE) and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain"},{"name":"11Department of Pediatric Endocrinology, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Mulero-Collantes","sequence":"additional","affiliation":[{"name":"12Department of Pediatrics, Hospital Universitario R\u00edo Hortega, Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C","family":"Barreda-Bonis","sequence":"additional","affiliation":[{"name":"4Skeletal Dysplasia Multidisciplinary Unit (UMDE) and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain"},{"name":"11Department of Pediatric Endocrinology, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Cruz-Rojo","sequence":"additional","affiliation":[{"name":"13Department of Pediatric Endocrinology, Hospital Universitario 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Ram\u00edrez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"14Department of Pediatrics, Hospital Universitario Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Berm\u00fadez de la Vega","sequence":"additional","affiliation":[{"name":"15Department of Pediatrics, Hospital Universitario Virgen de la Macarena, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4147-2800","authenticated-orcid":true,"given":"Andr\u00e9 M","family":"Travessa","sequence":"additional","affiliation":[{"name":"16Medical Genetics Service, Department of Pediatrics, Hospital de Santa Maria and Faculty of Medicine, University of Lisbon, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Gonz\u00e1lez de Buitrago Amigo","sequence":"additional","affiliation":[{"name":"17Department of Pediatrics, Hospital Universitario San Pedro de Alc\u00e1ntara, C\u00e1ceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-1619","authenticated-orcid":true,"given":"Angela","family":"del Pozo","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"5CIBERER, ISCIII, Madrid, Spain"},{"name":"6ERN-ITHACA, Hospital Universitario, Hospital La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8080-8629","authenticated-orcid":true,"given":"Elena","family":"Vallesp\u00edn","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"5CIBERER, ISCIII, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9108-2835","authenticated-orcid":true,"given":"Mario","family":"Sol\u00eds","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Goetz","sequence":"additional","affiliation":[{"name":"18PeRTICA SAS Consultant, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4649-2971","authenticated-orcid":true,"given":"\u00c1ngel","family":"Campos-Barros","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"5CIBERER, ISCIII, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-9118","authenticated-orcid":true,"given":"Fernando","family":"Santos-Simarro","sequence":"additional","affiliation":[{"name":"1Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain"},{"name":"4Skeletal Dysplasia Multidisciplinary Unit (UMDE) and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain"},{"name":"5CIBERER, ISCIII, Madrid, Spain"},{"name":"6ERN-ITHACA, Hospital Universitario, Hospital La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Gonz\u00e1lez-Casado","sequence":"additional","affiliation":[{"name":"4Skeletal Dysplasia Multidisciplinary Unit (UMDE) and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain"},{"name":"11Department of Pediatric Endocrinology, Hospital Universitario La Paz, Madrid, 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