{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:52:59Z","timestamp":1773028379256,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81100187"],"award-info":[{"award-number":["81100187"]}],"id":[{"id":"10.13039\/501100001809","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":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital aniridia is a severe ocular abnormality characterized by incomplete formation of the iris and many other ocular complications. Most cases are caused by the <jats:italic>paired box 6<\/jats:italic> (<jats:italic>PAX6<\/jats:italic>) gene mutations generating premature termination codons (PTCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ophthalmic examination was performed on a Chinese pedigree with congenital aniridia. The mutation was identified by targeted next\u2010generation sequencing. Nonsense suppression therapy was applied on patient\u2010derived lymphocytes. The <jats:italic>PAX6<\/jats:italic> expression was assayed by real\u2010time polymerase chain reaction and Western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Complete aniridia was complicated with horizontal nystagmus, contract, foveal hypoplasia, and microphthalmia. A novel heterozygous c.702_703delinsAT (p.Tyr234*) mutation was found in exon 9 of <jats:italic>PAX6<\/jats:italic>, generating a PTC at the homeodomain. There were about 50% reductions of both full\u2010length PAX6 protein and <jats:italic>PAX6<\/jats:italic> mRNA in patient\u2010derived lymphocytes, indicating haploinsufficiency due to nonsense\u2010mediated mRNA decay. Ataluren (PTC124) and geneticin (G418) could induce about 30%\u201340% translational readthrough. Nonsense suppression therapy restored PAX6 protein to about 65%\u201370% of unaffected family controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data expanded the genetic and phenotypic variations of congenital aniridia, and showed the therapeutic effect of nonsense suppression on this disease using patient\u2010derived cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1198","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T19:24:44Z","timestamp":1583263484000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Nonsense suppression induced readthrough of a novel <i>PAX6<\/i> mutation in patient\u2010derived cells of congenital aniridia"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8653-0907","authenticated-orcid":false,"given":"Xiaoliang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiming","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shengjing Hospital of China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601588"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2012.09.008"},{"key":"e_1_2_8_4_1","first-page":"1169","article-title":"Mutation analysis of paired box 6 gene in inherited aniridia in northern China","volume":"19","author":"Chen P.","year":"2013","journal-title":"Molecular Visision"},{"key":"e_1_2_8_5_1","first-page":"2139","article-title":"Eye anomalies and neurological manifestations in patients with PAX6 mutations","volume":"15","author":"Chien Y. 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