{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:26:26Z","timestamp":1747185986109,"version":"3.40.5"},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T00:00:00Z","timestamp":1720224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012155","name":"National Institute for Medical Research Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012155","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":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Neonatal diabetes mellitus (NDM) is a rare non\u2010immunological monogenic disorder characterized by hyperglycemic conditions primarily occurring within the first 6\u2009months of life. The majority of cases are attributed to pathogenic variants in genes affecting beta\u2010cell survival, insulin regulation, and secretion. This study aims to investigate the genetic landscape of NDM in Iran.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited a total of 135 patients who were initially diagnosed with diabetes at &lt;12\u2009months of age in Iran and referred to pediatric endocrinology clinics across the country. These patients underwent genetic diagnostic tests conducted by the Exeter Molecular Genetics Laboratory in the UK. The pathogenic variants identified were sorted and described based on type, pathogenicity (according to ACMG\/AMP criteria), novelty, and the affected protein domain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic defects were identified in 93 probands, presenting various pathogenic abnormalities associated with NDM and its associated syndromes. 76% of the patients were born as a result of consanguineous marriage, and a familial history of diabetes was found in 43% of the cases. A total of 58 distinct variants in 14 different genes were discovered, including 20 variants reported for the first time. Causative variants were most frequently identified in <jats:italic>EIF2AK3<\/jats:italic>, <jats:italic>KCNJ11<\/jats:italic>, and <jats:italic>ABCC8<\/jats:italic>, respectively. Notably, <jats:italic>EIF2AK3<\/jats:italic> and <jats:italic>ABCC8<\/jats:italic> exhibited the highest number of novel variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings provide valuable insights into the genetic landscape of NDM in the Iranian population and contribute to the knowledge of novel pathogenic variants within known causative genes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.14254","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T08:59:41Z","timestamp":1720256381000},"page":"1390-1402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic variant profiling of neonatal diabetes mellitus in Iranian patients: Unveiling 58 distinct variants in 14 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