{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T19:48:45Z","timestamp":1770752925182,"version":"3.50.0"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81561128015"],"award-info":[{"award-number":["81561128015"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81930019"],"award-info":[{"award-number":["81930019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p><jats:italic>PAX6<\/jats:italic> is a transcription factor involved in embryonic development of many organs, including the eyes and the pancreas. Mutations of <jats:italic>PAX6<\/jats:italic> gene is the main cause of a rare disease, congenital aniridia (CA). This case\u2013control study aims to investigate the effects of <jats:italic>PAX6<\/jats:italic> mutations on glucose metabolism and insulin secretion in families with CA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In all, 21 families with CA were screened by Sanger sequencing. Patients with <jats:italic>PAX6<\/jats:italic> mutations and CA (cases) and age\u2010matched healthy family members (controls) were enrolled. Oral glucose tolerance test (OGTT) was performed to detect diabetes or impaired glucose tolerance (IGT). Insulin and proinsulin secretion were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 21 CA families, heterozygous <jats:italic>PAX6<\/jats:italic> mutations were detected in five families. Among cases (<jats:italic>n<\/jats:italic>\u00a0=\u00a010) from the five families, two were diagnosed with newly identified diabetes and another two were diagnosed with IGT. Among controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a012), two had IGT. The levels of haemoglobin A1c were 36\u00a0\u00b1\u00a04\u00a0mmol\/mol (5.57\u00a0\u00b1\u00a00.46%) and 32\u00a0\u00b1\u00a05\u00a0mmol\/L (5.21\u00a0\u00b1\u00a00.54%) in the cases and the controls, respectively (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.049). More importantly, levels of proinsulin in the cases were significantly higher than that of the controls, despite similar levels of total insulin. The areas under the curve of proinsulin in the cases (6425\u00a0\u00b1\u00a04390) were significantly higher than that of the controls (3709\u00a0\u00b1\u00a01769) (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.032).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>PAX6<\/jats:italic> may participate in the production of proinsulin to insulin and heterozygous <jats:italic>PAX6<\/jats:italic> mutations may be associated with glucose metabolism in CA patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.14456","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T21:21:00Z","timestamp":1605043260000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Heterozygous <i>PAX6<\/i> mutations may lead to hyper\u2010proinsulinaemia and glucose intolerance: A case\u2013control study in families with congenital aniridia"],"prefix":"10.1111","volume":"38","author":[{"given":"Wei","family":"Tian","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Diabetes Research and Care Department of Endocrinology Beijing Tongren Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Rong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diabetes Research and Care Department of Endocrinology Beijing Tongren Hospital Capital Medical University Beijing China"},{"name":"Beijing Diabetes Institute Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun\u2010Yan","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Beijing Tongren Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying\u2010Nan","family":"Ma","sequence":"additional","affiliation":[{"name":"Beijing Institute of Ophthalmology Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang\u2010Yuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diabetes Research and Care Department of Endocrinology Beijing Tongren Hospital Capital Medical University Beijing China"},{"name":"Beijing Diabetes Institute Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Mathematics School of Biomedical Engineering Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian\u2010Ping","family":"Feng","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diabetes Research and Care Department of Endocrinology Beijing Tongren Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diabetes Research and Care Department of Endocrinology Beijing Tongren Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong\u2010Rong","family":"Xie","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diabetes Research and Care Department of Endocrinology Beijing Tongren Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Lu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diabetes Research and Care Department of Endocrinology Beijing Tongren Hospital Capital Medical University Beijing China"},{"name":"Beijing Diabetes Institute Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Cao","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diabetes Research and Care Department of Endocrinology Beijing Tongren Hospital Capital Medical University Beijing China"},{"name":"Beijing Diabetes Institute Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian\u2010Bo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diabetes Research and Care Department of Endocrinology Beijing Tongren Hospital Capital Medical University Beijing China"},{"name":"Beijing Diabetes Institute Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5430-2149","authenticated-orcid":false,"given":"Jin\u2010Kui","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diabetes Research and Care Department of Endocrinology Beijing Tongren Hospital Capital Medical University Beijing China"},{"name":"Beijing Diabetes Institute Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1464"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00346"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S179793"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d6044"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(96)80087-1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2017.1257000"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7914031"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1192-232"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0000000000000405"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/13816810.2015.1059459"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.1.224"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2005.01469.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1210-x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12251"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12902"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.12.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2019.1649704"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12109"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.784629"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI88015"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12524"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1932296818805074"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcjo.2017.04.006"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13019"},{"key":"e_1_2_9_26_1","first-page":"2139","article-title":"Mutation spectrum of PAX6 in Chinese patients with aniridia","volume":"17","author":"Zhang X","year":"2011","journal-title":"Mol Vis"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1425"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2000.15.3.195"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2019.04.044"}],"container-title":["Diabetic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.14456","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dme.14456","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.14456","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T15:29:49Z","timestamp":1693582189000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dme.14456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1111\/dme.14456"],"URL":"https:\/\/doi.org\/10.1111\/dme.14456","archive":["Portico"],"relation":{},"ISSN":["0742-3071","1464-5491"],"issn-type":[{"value":"0742-3071","type":"print"},{"value":"1464-5491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"2020-06-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14456"}}