{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:56:12Z","timestamp":1777928172807,"version":"3.51.4"},"reference-count":77,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"\n Maturity-onset diabetes of the young (MODY) is a highly heterogeneous group of monogenic and nonautoimmune diseases. Misdiagnosis of MODY is a widespread problem and about 5% of patients with type 2 diabetes mellitus and nearly 10% with type 1 diabetes mellitus may actually have MODY. Using next-generation DNA sequencing (NGS) to facilitate accurate diagnosis of MODY, this study investigated mutations in 13 MODY genes (\n HNF4A<\/jats:italic>\n ,\n GCK<\/jats:italic>\n ,\n HNF1A<\/jats:italic>\n ,\n PDX1<\/jats:italic>\n ,\n HNF1B<\/jats:italic>\n ,\n NEUROD1<\/jats:italic>\n ,\n KLF11<\/jats:italic>\n ,\n CEL<\/jats:italic>\n ,\n PAX4<\/jats:italic>\n ,\n INS<\/jats:italic>\n ,\n BLK<\/jats:italic>\n ,\n ABCC8<\/jats:italic>\n , and\n KCNJ11<\/jats:italic>\n ). In addition, we comprehensively investigated the clinical phenotypic effects of the genetic variations identified. Fifty-one adult patients with suspected MODY and 64 healthy controls participated in the study. We identified 7 novel and 10 known missense mutations localized in\n PDX1<\/jats:italic>\n ,\n HNF1B<\/jats:italic>\n ,\n KLF11<\/jats:italic>\n ,\n CEL<\/jats:italic>\n ,\n BLK<\/jats:italic>\n , and\n ABCC8<\/jats:italic>\n genes in 29.4% of the patient sample. Importantly, we report several mutations that were classified as \u201cdeleterious\u201d as well as those predicted as \u201cbenign.\u201d Notably, the\n ABCC8<\/jats:italic>\n p.R1103Q,\n ABCC8<\/jats:italic>\n p.V421I,\n CEL<\/jats:italic>\n I336T,\n CEL<\/jats:italic>\n p.N493H,\n BLK<\/jats:italic>\n p.L503P,\n HNF1B<\/jats:italic>\n p.S362P, and\n PDX1<\/jats:italic>\n p.E69A mutations were identified for the first time as causative variants for MODY. More aggressive clinical features were observed in three patients with double- and triple-heterozygosity of\n PDX1<\/jats:italic>\n -\n KLF11<\/jats:italic>\n (p.E69A\/p.S182R),\n CEL<\/jats:italic>\n -\n ABCC8<\/jats:italic>\n -\n KCNJ11<\/jats:italic>\n (p.I336, p.G157R\/p.R1103Q\/p.A157A), and\n HNF1B<\/jats:italic>\n -\n KLF11<\/jats:italic>\n (p.S362P\/p.P261L). Interestingly, the clinical effects of the\n BLK<\/jats:italic>\n mutations appear to be exacerbated in the presence of obesity. In conclusion, NGS analyses of the adult patients with suspected MODY appear to be informative in a clinical context. These findings warrant further clinical diagnostic research and development in different world populations suffering from diabetes with genetic underpinnings.\n <\/jats:p>","DOI":"10.1089\/omi.2022.0006","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T16:30:22Z","timestamp":1648225822000},"page":"218-235","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Precision Diagnosis of Maturity-Onset Diabetes of the Young with Next-Generation Sequencing: Findings from the MODY-IST Study in Adult Patients"],"prefix":"10.1177","volume":"26","author":[{"given":"Hulya Yilmaz","family":"Aydogan","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, 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Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gizem","family":"Gulfidan","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6036-1348","authenticated-orcid":false,"given":"Kazim Yalcin","family":"Arga","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey."},{"name":"Genetic and Metabolic Diseases Research and Investigation Center, Marmara University, Istanbul, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aclan","family":"Ozder","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet 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