{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:55:57Z","timestamp":1790999757120,"version":"4.1.0"},"reference-count":23,"publisher":"Japanese Society for Pediatric Endocrinology","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pediatr Endocrinol"],"published-print":{"date-parts":[[2026]]},"DOI":"10.1297\/cpe.2026-0014","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T22:09:30Z","timestamp":1779314970000},"page":"351-356","source":"Crossref","is-referenced-by-count":0,"title":["Family with two novel &lt;i&gt;in cis&lt;\/i&gt; &lt;i&gt;INSR&lt;\/i&gt; gene variants: Phenotypic evolution with age"],"prefix":"10.1297","volume":"35","author":[{"given":"Georgia","family":"Sotiriou","sequence":"first","affiliation":[{"name":"1<sup>st<\/sup> Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anny","family":"Mertzanian","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School, \u201cAghia Sophia\u201d Children\u2019s Hospital, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eleni","family":"Raptopoulou","sequence":"additional","affiliation":[{"name":"1<sup>st<\/sup> Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Sertedaki","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School, \u201cAghia Sophia\u201d Children\u2019s Hospital, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tsirevelou","sequence":"additional","affiliation":[{"name":"1<sup>st<\/sup> Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eftychia","family":"Drogouti","sequence":"additional","affiliation":[{"name":"Second Department of Neonatology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina Kanaka","family":"Gantenbein","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, ENDO-ERN Center for Rare Paediatric Endocrine Diseases, First Department of Pediatrics, Medical School, \u201cAghia Sophia\u201d Children\u2019s Hospital, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Tsakalidis","sequence":"additional","affiliation":[{"name":"Second Department of Neonatology, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Christoforidis","sequence":"additional","affiliation":[{"name":"1<sup>st<\/sup> Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"125","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Kahn, CR, Flier, JS, Bar, RS, Archer, JA, Gorden, P, Martin, MM, et al. The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med 1976;294: 739\u201345.","DOI":"10.1056\/NEJM197604012941401"},{"key":"2","doi-asserted-by":"publisher","unstructured":"2. Hosoe, J, Kadowaki, H, Miya, F, Aizu, K, Kawamura, T, Miyata, I, et al. Structural basis and genotype-phenotype correlations of INSR mutations causing severe insulin resistance. Diabetes 2017;66: 2713\u201323.","DOI":"10.2337\/db17-0301"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Longo, N, Wang, Y, Smith, SA, Langley, SD, DiMeglio, LA, Giannella-Neto, D. Genotype-phenotype correlation in inherited severe insulin resistance. Hum Mol Genet 2002;11: 1465\u201375.","DOI":"10.1093\/hmg\/11.12.1465"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Collin-Chavagnac, D, Saint-Martin, C, Bedidi, L, Lebreton, L, Aslanzadeh, V, Vigouroux, C, et al. Insulin receptor variants: extending the traditional mendelian spectrum. Genet Med 2025;27: 101404.","DOI":"10.1016\/j.gim.2025.101404"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Takasawa, K, Tsuji-Hosokawa, A, Takishima, S, Wada, Y, Nagasaki, K, Dateki, S, et al. Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the b-subunit of the insulin receptor (INSR) gene. J Diabetes 2019;11: 46\u201354.","DOI":"10.1111\/1753-0407.12797"},{"key":"6","unstructured":"6. Mesika, A, Klar, A, Falik Zaccai, TC. <i>INSR<\/i>-Related Severe Insulin Resistance Syndrome. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews\u00ae. Seattle (WA): University of Washington, Seattle; January 25,  2018."},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Yuan, X, Zhu, Z, Liang, C. Genealogical Rabson-Mendenhall syndrome caused by <i>INSR<\/i> gene mutation. Am J Physiol Endocrinol Metab 2025;329: E227\u201332.","DOI":"10.1152\/ajpendo.00285.2024"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Huang, Z, Li, Y, Tang, T, Xu, W, Liao, Z, Yao, B, et al. Hyperinsulinaemic hypoglycaemia associated with a heterozygous missense mutation of R1174W in the insulin receptor (IR) gene. Clin Endocrinol (Oxf) 2009;71: 659\u201365.","DOI":"10.1111\/j.1365-2265.2009.03525.x"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Imamovic, M, V\u00e5gberg, M, Cederquist, K, Dahlqvist, P. Hyperinsulinemic hypoglycemia in a patient with a mutation in the insulin receptor. JCEM Case Rep 2024;2: luae221.","DOI":"10.1210\/jcemcr\/luae221"},{"key":"10","unstructured":"10. Poon, SWY, Chung, BHY, Wong, MSC, Tsang, AMC. Diazoxide-unresponsive hyperinsulinemic hypoglycaemia in a preterm infant with heterozygous insulin receptor gene mutation. J Clin Res Pediatr Endocrinol 2025;17: 115\u20139."},{"key":"11","doi-asserted-by":"publisher","unstructured":"11. H\u00f8jlund, K, Hansen, T, Lajer, M, Henriksen, JE, Levin, K, Lindholm, J, et al. A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. Diabetes 2004;53: 1592\u20138.","DOI":"10.2337\/diabetes.53.6.1592"},{"key":"12","unstructured":"12. Abramowski, A, Ward, R, Hamdan, AH. Neonatal Hypoglycemia. In: <i>StatPearls<\/i>. Treasure Island (FL): StatPearls Publishing; September 4,  2023."},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Thornton, PS, Stanley, CA, De Leon, DD, Harris, D, Haymond, MW, Hussain, K, et al. Pediatric Endocrine Society. Recommendations from the pediatric endocrine society for evaluation and management of persistent hypoglycemia in neonates, infants, and children. J Pediatr 2015;167: 238\u201345.","DOI":"10.1016\/j.jpeds.2015.03.057"},{"key":"14","doi-asserted-by":"publisher","unstructured":"14. Ebina, Y, Ellis, L, Jarnagin, K, Edery, M, Graf, L, Clauser, E, et al. The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. Cell 1985;40: 747\u201358.","DOI":"10.1016\/0092-8674(85)90334-4"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Aslanzadeh, V, Brierley, GV, Kumar, R, \u00c7ubuk, H, Vigouroux, C, Matreyek, KA, et al. Deep mutational scanning of the human insulin receptor ectodomain to inform precision therapy for insulin resistance. Nat Commun 2025;16: 9143.","DOI":"10.1038\/s41467-025-64178-4"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Longo, N, Wang, Y, Smith, SA, Langley, SD, DiMeglio, LA, Giannella-Neto, D. Genotype-phenotype correlation in inherited severe insulin resistance. Hum Mol Genet 2002;11: 1465\u201375.","DOI":"10.1093\/hmg\/11.12.1465"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Preumont, V, Feincoeur, C, Lascols, O, Courtillot, C, Touraine, P, Maiter, D, et al. Hypoglycaemia revealing heterozygous insulin receptor mutations. Diabetes Metab 2017;43: 95\u20136.","DOI":"10.1016\/j.diabet.2016.07.001"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Innaurato, S, Brierley, GV, Grasso, V, Massimi, A, Gaudino, R, Sileno, S, et al. Severe insulin resistance in disguise: A familial case of reactive hypoglycemia associated with a novel heterozygous INSR mutation. Pediatr Diabetes 2018;19: 670\u20134.","DOI":"10.1111\/pedi.12632"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Sethi, A, Foulds, N, Ehtisham, S, Ahmed, SH, Houghton, J, Colclough, K, et al. Heterozygous insulin receptor <i>(INSR)<\/i> mutation associated with neonatal hyperinsulinemic hypoglycaemia and familial diabetes mellitus: case series. J Clin Res Pediatr Endocrinol 2020;12: 420\u20136.","DOI":"10.4274\/jcrpe.galenos.2019.2019.0106"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Krishnamurthy, M, Pingul, MM. A novel insulin receptor mutation in an adolescent with acanthosis nigricans and hyperandrogenism. J Pediatr Endocrinol Metab 2016;29: 1201\u20135.","DOI":"10.1515\/jpem-2015-0384"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Enkhtuvshin, B, Nagashima, S, Saito, N, Wakabayashi, T, Ando, A, Takahashi, M, et al. Successful pregnancy outcomes in a patient with type A insulin resistance syndrome. Diabet Med 2015;32: e16\u20139.","DOI":"10.1111\/dme.12659"},{"key":"22","unstructured":"22. Jialal, I, Basheer, H. Syndromes of autoantibodies to the insulin receptor. Int J Biochem Mol Biol 2022;13: 87\u201391."},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Delacruz, L, Adamczak, LJ, Astapova, O. Postprandial hypoglycemia associated with <i>insulin receptor<\/i> gene variant G1146R. JCEM Case Rep 2025;3: luaf247.","DOI":"10.1210\/jcemcr\/luaf247"}],"container-title":["Clinical Pediatric Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/cpe\/35\/4\/35_2026-0014\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:40:36Z","timestamp":1790998836000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/cpe\/35\/4\/35_2026-0014\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1297\/cpe.2026-0014","relation":{},"ISSN":["0918-5739","1347-7358"],"issn-type":[{"value":"0918-5739","type":"print"},{"value":"1347-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"2026-0014"}}