{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:03:27Z","timestamp":1777644207215,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>SHOX<\/jats:italic> enhancer CNVs, affecting one or more of the seven recognized evolutionary conserved non\u2010coding elements (CNEs) represent one of the most frequent cause of <jats:italic>SHOX<\/jats:italic>\u2010haploinsufficiency. During the diagnostic workflow deletions\/duplications have been identified downstream <jats:italic>SHOX<\/jats:italic> not including any of the these CNEs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fine tiling aCGH and breakpoint PCR were used to characterize the critical interval and to search for novel alterations in a cohort of selected patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Screening of 252 controls provided evidence that duplications in this area represent likely benign variants whereas none of the deletions were detected. These findings suggested that other alterations relevant for <jats:italic>SHOX<\/jats:italic>\u2010haploinsufficiency might be missed by the standard diagnostic methods. To identify such undisclosed elements, the aCGH was used to reanalyze 52 unresolved cases with clinical features strongly suggestive of <jats:italic>SHOX<\/jats:italic>\u2010haploinsufficiency. This analysis followed by the screening of 210 patients detected two partially overlapping small deletions of ~12 and ~8\u00a0kb in four unrelated individuals, approximately 15\u00a0kb downstream <jats:italic>SHOX<\/jats:italic>, that were absent in 720 normal stature individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results strengthen the hypothesis that alterations of yet unidentified cis\u2010regulatory elements residing outside those investigated through conventional methods, might explain the phenotype in ISS\/LWD patients thus enlarging the spectrum of variants contributing to <jats:italic>SHOX<\/jats:italic>\u2010haploinsufficiency.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1793","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T08:06:11Z","timestamp":1637654771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and L\u00e9ri\u2010Weill dyschondrosteosis"],"prefix":"10.1002","volume":"10","author":[{"given":"Antonella","family":"Fanelli","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze della Salute Universit\u00e0 del Piemonte Orientale Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Vannelli","sequence":"additional","affiliation":[{"name":"Endocrinologia Pediatrica Dipartimento di Pediatria e Specialit\u00e0 Pediatriche Ospedale Regina Margherita Citta della Salute e della Scienza Torino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak","family":"Babu","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute Universit\u00e0 del Piemonte Orientale Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Mellone","sequence":"additional","affiliation":[{"name":"Laboratorio di Genetica S.C.D.U Biochimica Clinica Azienda Ospedaliera Universitaria \"Maggiore della Carit\u00e0\" Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Cucci","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute Universit\u00e0 del Piemonte Orientale Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Monzani","sequence":"additional","affiliation":[{"name":"Divisione di Pediatria AOU \"Maggiore della Carit\u00e0\" Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wael","family":"Al Essa","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute Universit\u00e0 del Piemonte Orientale Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Secco","sequence":"additional","affiliation":[{"name":"SC Pediatria e DEA Pediatrico Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo Alessandria Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Follenzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute Universit\u00e0 del Piemonte Orientale Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simonetta","family":"Bellone","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute Universit\u00e0 del Piemonte Orientale Novara Italy"},{"name":"Divisione di Pediatria AOU \"Maggiore della Carit\u00e0\" Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Prodam","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute Universit\u00e0 del Piemonte Orientale Novara Italy"},{"name":"Divisione di Endocrinologia AOU \u201cMaggiore della Carit\u00e0\u201d Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6686-4600","authenticated-orcid":false,"given":"Mara","family":"Giordano","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute Universit\u00e0 del Piemonte Orientale Novara Italy"},{"name":"Laboratorio di Genetica S.C.D.U Biochimica Clinica Azienda Ospedaliera Universitaria \"Maggiore della Carit\u00e0\" Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010020\u20100676\u2010y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1689"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100678"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2006.04.004"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.650"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006\u20101409"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph7031047"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37524"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35919"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36724"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03344156"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u2010213X\u201011\u201063"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2008.07.009"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.216"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/499254"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.53"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.247"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004503"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.06.034"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.35"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021498"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010018\u20100445\u20108"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61275"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33334"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.046581"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl470"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2016.18"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201032565\u20101"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32914"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36284"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep17667"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1793","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1793","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1793","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T03:18:40Z","timestamp":1693192720000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,23]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/mgg3.1793"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1793","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,23]]},"assertion":[{"value":"2020-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1793"}}