{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:37:45Z","timestamp":1791041865619,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T00:00:00Z","timestamp":1530662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP17am0101111"],"award-info":[{"award-number":["JP17am0101111"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Type A insulin resistance (IR) is a rare form of severe congenital IR that is frequently caused by heterozygous mutations in the insulin receptor (<jats:italic>INSR<\/jats:italic>) gene. Although Type A IR requires appropriate intervention from the early stages of diabetes, proper diagnosis of this disease is challenging, and accumulation of cases with detailed clinical profiles and genotypes is required.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Herein we report on six peripubertal patients with clinically diagnosed Type A IR, including four patients with an identified <jats:italic>INSR<\/jats:italic> mutation. To clarify the clinical features of Type A IR due to <jats:italic>INSR<\/jats:italic> mutation, we validated the clinical characteristics of Type A IR patients with identified <jats:italic>INSR<\/jats:italic> mutations by comparing them with mutation\u2010negative patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four heterozygous missense mutations within the \u03b2\u2010subunit of INSR were detected: Gly1146Arg, Arg1158Trp, Arg1201Trp, and one novel Arg1201Pro mutation. There were no obvious differences in clinical phenotypes, except for normal lipid metabolism and autosomal dominant inheritance, between Type A IR due to <jats:italic>INSR<\/jats:italic> mutations and Type A IR due to other factors. However, our analysis revealed that the extent of growth retardation during the fetal period is correlated with the severity of insulin signaling impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study details the clinical features of four patients with genetically proven Type A IR. Further accumulation of genetically proven cases and long\u2010term treatment prognoses following early diagnosis are required to further elucidate the dynamics of this disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.12797","type":"journal-article","created":{"date-parts":[[2018,6,7]],"date-time":"2018-06-07T02:55:02Z","timestamp":1528340102000},"page":"46-54","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the \u03b2\u2010subunit of the insulin receptor (<i>INSR<\/i>) gene"],"prefix":"10.1111","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-4034","authenticated-orcid":false,"given":"Kei","family":"Takasawa","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Developmental Biology Tokyo Medical and Dental University  Tokyo 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