{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:09:58Z","timestamp":1777370998622,"version":"3.51.4"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81170736, 81570715, 81870579"],"award-info":[{"award-number":["81170736, 81570715, 81870579"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>Neonatal diabetes mellitus is created by alterations in the genes responsible for beta\u2010cell mass and\/or function. The present study aimed to evaluate the genetic variants in the insulin gene (<jats:italic>INS<\/jats:italic>) in four Chinese infants aged &lt;12\u00a0months with diabetes onset, and to explore the clinical and genetic characteristics of permanent neonatal diabetes mellitus caused by <jats:italic>INS<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The complete coding sequences of <jats:italic>KCNJ11, ABCC8<\/jats:italic> and <jats:italic>INS<\/jats:italic> were detected using Sanger sequencing. The pathogenicity of the mutations was determined based on the American College of Medical Genetics and Genomics, and the structure of wild\u2010type and mutant proteins was predicted using the web\u2010based tool, Phyre2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One novel mutation (p.I99_C100insSI) and three previously reported variants (p.G32S, p.R89C and p.C96R) in <jats:italic>INS<\/jats:italic> were identified in four infants with early\u2010onset diabetes. All the mutations in the four patients were de novo. Except for mutation R89C, which causes permanent neonatal diabetes mellitus through the addition of an additional cysteine residue at the cleavage site of the A chain and C\u2010peptide, the other three mutations affected disulfide bonds. The patients had diabetes with marked hyperglycemia or diabetic ketoacidosis, and were then treated with exogenous insulin. Mutations in crucial regions of the <jats:italic>INS<\/jats:italic> might give rise to diabetes with varying severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study enriches our awareness of the mutant spectrum in <jats:italic>INS<\/jats:italic>, and suggests the important role of <jats:italic>INS<\/jats:italic> in the development of permanent neonatal diabetes mellitus.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13156","type":"journal-article","created":{"date-parts":[[2019,10,12]],"date-time":"2019-10-12T18:28:17Z","timestamp":1570904897000},"page":"578-584","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of insulin gene variants in patients with neonatal diabetes in the Chinese population"],"prefix":"10.1111","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0129-519X","authenticated-orcid":false,"given":"Junling","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Endocrinology NHC Key Laboratory of Endocrinology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology NHC Key Laboratory of Endocrinology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingmin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology NHC Key Laboratory of Endocrinology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinhua","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology NHC Key Laboratory of Endocrinology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 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