{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T08:12:32Z","timestamp":1780733552924,"version":"3.54.1"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Stickler syndrome (SS) is a hereditary connective tissue disorder affecting bones, eyes, and hearing. Type 2 SS and the SS variant otospondylomegaepiphyseal dysplasia (OSMED) are caused by deleterious variants in COL11A1 and COL11A2, respectively. In both genes, available database information indicates a high rate of potentially deleterious intronic variants, but published evidence of their biological effect is usually insufficient for a definite clinical interpretation. We report four previously unpublished intronic variants in COL11A1 (c.2241 + 5G&gt;T, c.2809 \u2212 2A&gt;G, c.3168 + 5G&gt;C) and COL11A2 (c.4392 + 1G&gt;A) identified in type 2 SS\/OSMED individuals. The pathogenic effect of these variants was first predicted in silico and then investigated by an exon-trapping assay. We demonstrated that all variants can induce exon in-frame deletions, which lead to the synthesis of shorter collagen XI \u03b11 or 2 chains. Lacking residues are located in the \u03b1-triple helical region, which has a crucial role in regulating collagen fibrillogenesis. In conclusion, this study suggests that these alternative COL11A1 and COL11A2 transcripts might result in aberrant triple helix collagen. Our approach may help to improve the diagnostic molecular pathway of COL11-related disorders.<\/jats:p>","DOI":"10.3390\/genes11121513","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T21:21:49Z","timestamp":1608240109000},"page":"1513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Exon-Trapping Assay Improves Clinical Interpretation of COL11A1 and COL11A2 Intronic Variants in Stickler Syndrome Type 2 and Otospondylomegaepiphyseal Dysplasia"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-194X","authenticated-orcid":false,"given":"Lucia","family":"Micale","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1094-1774","authenticated-orcid":false,"given":"Silvia","family":"Morlino","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Schirizzi","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6543-6225","authenticated-orcid":false,"given":"Emanuele","family":"Agolini","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, IRCCS-Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Nardella","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Fusco","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Castellana","sequence":"additional","affiliation":[{"name":"Unit of Bioinformatics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Guarnieri","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Villa","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6723-9177","authenticated-orcid":false,"given":"Maria Francesca","family":"Bedeschi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Grammatico","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, 00152 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, IRCCS-Bambino Ges\u00f9 Children\u2019s Hospital, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Castori","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1136\/jmg.36.5.353","article-title":"Clinical and Molecular genetics of Stickler syndrome","volume":"36","author":"Snead","year":"1999","journal-title":"J. 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