{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:28:01Z","timestamp":1790015281236,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2019JJ40408"],"award-info":[{"award-number":["2019JJ40408"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2021JJ40811"],"award-info":[{"award-number":["2021JJ40811"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Stickler syndrome is a multisystemic disorder characterized by ophthalmological and non\u2010ophthalmological abnormalities, frequently misdiagnosed due to high clinical heterogeneity. Stickler syndrome type I (STL1) is predominantly caused by mutations in the <jats:italic>COL2A1<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exome sequencing and co\u2010segregation analysis were utilized to scrutinize 35 families with high myopia, and pathogenic mutations were identified. Mutant COL2A1 was overexpressed in cells for mechanistic study. A retrospective genotype\u2013phenotype correlation analysis was further conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two novel pathogenic mutations (c.2895+1G&gt;C and c.3505G&gt;A (p.Val1169Ile)) and two reported mutations (c.1597C&gt;T (p.Arg533*) and c.1693C&gt;T (p.Arg565Cys)) in <jats:italic>COL2A1<\/jats:italic> were identified causing STL1. These mutations are all in the G\u2010X\u2010Y triplet, and c.2895+1G&gt;C contributed to aberrant RNA splicing. COL2A1 mutants tended to form large aggregates in the endoplasmic reticulum (ER) and elevated ER stress. Additionally, mutations c.550G&gt;A (p.Ala184Thr) and c.2806G&gt;A (p.Gly936Ser) in <jats:italic>COL2A1<\/jats:italic> were found in high myopia families, but were likely benign, although c.2806G&gt;A (p.Gly936Ser) is on G\u2010X\u2010Y triplet. Moreover, genotype\u2013phenotype correlation analysis revealed that mutations in exon 2 mainly contribute to retinal detachment, whereas mutations in the collagen alpha\u20101 chain region of COL2A1 tend to cause non\u2010ophthalmologic symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study broadens the <jats:italic>COL2A1<\/jats:italic> gene mutation spectrum, provides evidence for ER stress caused by pathogenic COL2A1 mutations and highlights the importance of non\u2010ophthalmological examination in clinical diagnosis of high myopia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2331","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T09:41:19Z","timestamp":1702287679000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exome sequencing\u2010aided precise diagnosis of four families with type I Stickler syndrome"],"prefix":"10.1002","volume":"12","author":[{"given":"Runyi","family":"Tian","sequence":"first","affiliation":[{"name":"Center for Medical Genetics, School of Life Sciences Central South University  Changsha China"},{"name":"Institute of Molecular Precision Medicine Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Molecular Precision Medicine Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyu","family":"Zang","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, School of Life Sciences Central 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