{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:38:16Z","timestamp":1791041896831,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["18K07895"],"award-info":[{"award-number":["18K07895"]}],"id":[{"id":"10.13039\/501100001700","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":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>To investigate the genetic background of Japanese patients with suspected maturity\u2010onset diabetes of the young (MODY).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>On 340 proband patients referred from across Japan, genomic variants were analyzed using a targeted multigene panel analysis combined with the multiplex ligation probe amplification (MLPA) analysis, mitochondrial m.3243A\u2009&gt;\u2009G analysis and methylation\u2010specific polymerase chain reaction of the imprinted 6q24 locus. Pathogenic\/likely pathogenic variants were listed according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Additionally, variants with a population frequency &lt;0.001 and Combined Annotation Dependent Depletion score\u2009&gt;20 (CS &gt;20) were listed as rare variants of uncertain significance\u2010CS\u2009&gt;20.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 157 pathogenic\/likely pathogenic variants and 44 rare variants of uncertain significance\u2010CS\u2009&gt;20 were identified. In the pathogenic\/likely pathogenic variants, alterations in the <jats:italic>GCK<\/jats:italic> gene were the most common (82, 52.2%) followed by <jats:italic>HNF1A<\/jats:italic> (29,\u00a018.5%), <jats:italic>HNF4A<\/jats:italic> (13, 8.3%) and <jats:italic>HNF1B<\/jats:italic> (13, 8.3%). One patient was a 29.5% mosaic with a truncating <jats:italic>INSR<\/jats:italic> variant. In the rare variants of uncertain significance\u2010CS\u2009&gt;20, 20 (45.5%) were in the genes coding for the adenosine triphosphate\u2010sensitive potassium channel, <jats:italic>KCNJ11<\/jats:italic> or <jats:italic>ABCC8<\/jats:italic>, and four were in the genes of the insulin\u2010signaling pathway, <jats:italic>INSR<\/jats:italic> and <jats:italic>PIK3R1<\/jats:italic>. Four variants in <jats:italic>ABCC8<\/jats:italic> were previously reported in patients with congenital hyperinsulinism, suggesting the inactivating nature of these variants, and at least two of our patients had a history of congenital hyperinsulinism evolving into diabetes. In two patients with <jats:italic>INSR<\/jats:italic> or <jats:italic>PIK3R1<\/jats:italic> variants, insulin resistance was evident at diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Causative genomic variants could be identified in at least 46.2% of clinically suspected MODY patients. <jats:italic>ABCC8<\/jats:italic>\u2010MODY with inactivating variants could represent a distinct category of MODY. Genes of insulin resistance should be included in the sequencing panel for MODY.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13957","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T09:00:20Z","timestamp":1670835620000},"page":"387-403","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Targeted gene panel analysis of Japanese patients with maturity\u2010onset diabetes of the young\u2010like diabetes mellitus: Roles of inactivating variants in the <scp><i>ABCC8<\/i><\/scp> and insulin resistance genes"],"prefix":"10.1111","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8945-4775","authenticated-orcid":false,"given":"Tohru","family":"Yorifuji","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology and Metabolism Children's Medical Center, Osaka City General Hospital  Osaka Japan"},{"name":"Department of Genetic Medicine Osaka City General 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