{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T23:40:44Z","timestamp":1782344444369,"version":"3.54.5"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"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><jats:bold>Background:<\/jats:bold> Stickler syndrome (SS) is a group of hereditary collagenopathies caused by a variety of collagen and non-collagen genes. Affected patients have characteristic manifestations involving ophthalmic, articular, craniofacial and auditory disorders. SS is classified into several subtypes according to clinical and molecular features. Type 3 SS is an ultra-rare disease, known as non-ocular SS or otospondylomegaepiphyseal dysplasia (OSMED) with only a few pathogenic <jats:italic>COL11A2<\/jats:italic> variants reported to date.<\/jats:p><jats:p><jats:bold>Case presentation:<\/jats:bold> A 29-year-old Chinese male was referred to our hospital for hearing loss and multiple joint pain. He presented a phenotype highly suggestive of OSMED, including progressive sensorineural deafness, spondyloepiphyseal dysplasia with large epiphyses, platyspondyly, degenerative osteoarthritis, and sunken nasal bridge. We detected compound heterozygous mutations in <jats:italic>COL11A2<\/jats:italic>, both of which were predicted to be splicing mutations. One is synonymous mutation c.3774C&amp;gt;T (p.Gly1258Gly) supposed to be a splice site mutation, the other is a novel intron mutation c.4750 + 5\u00a0G&amp;gt;A, which is a highly conservative site across several species. We also present a review of the current known pathogenic mutation spectrum of <jats:italic>COL11A2<\/jats:italic> in patients with type 3 SS.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Both synonymous extonic and intronic variants are easily overlooked by whole-exome sequencing. For patients with clinical manifestations suspected of SS syndrome, next-generation whole-genome sequencing is necessary for precision diagnosis and genetic counseling.<\/jats:p>","DOI":"10.3389\/fgene.2023.1154087","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T16:27:35Z","timestamp":1686068855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case report: Autosomal recessive type 3 Stickler syndrome caused by compound heterozygous mutations in COL11A2"],"prefix":"10.3389","volume":"14","author":[{"given":"Ying","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Qiong","family":"Ran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe-Long","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Hong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Feng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Tao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.ymgme.2014.09.001","article-title":"Novel pathogenic COL11A1\/COL11A2 variants in Stickler syndrome detected by targeted NGS and exome sequencing","volume":"1133","author":"Acke","year":"2014","journal-title":"Mol. 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