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Genetic Variant Profiling of Neonatal Diabetes Mellitus in Iranian Patients: Unveiling 58 Distinct Variants in 14 Genes Publisher Pubmed



Mianesaz H1, 2 ; Ghalamkari S2, 3 ; Abbasi F4 ; Razzaghyazar M5 ; Sayarifard F4 ; Vakili R6 ; Sedghi M2, 7 ; Noroozi Asl S7 ; Hosseini S7 ; Amoli MM5 ; Yaghootkar H8
Authors
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Authors Affiliations
  1. 1. Department of Human Genetics, Medical School, University of Debrecen, Debrecen, Hungary
  2. 2. Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  4. 4. Growth and Development Research Center, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular – Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pediatric Endocrinology and Metabolism, Faculty of Medicine, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
  7. 7. Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. College of Health and Science, University of Lincoln, Lincoln, United Kingdom

Source: Journal of Diabetes Investigation Published:2024


Abstract

Introduction: Neonatal diabetes mellitus (NDM) is a rare non-immunological monogenic disorder characterized by hyperglycemic conditions primarily occurring within the first 6 months of life. The majority of cases are attributed to pathogenic variants in genes affecting beta-cell survival, insulin regulation, and secretion. This study aims to investigate the genetic landscape of NDM in Iran. Methods: We recruited a total of 135 patients who were initially diagnosed with diabetes at <12 months 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. Results: 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 EIF2AK3, KCNJ11, and ABCC8, respectively. Notably, EIF2AK3 and ABCC8 exhibited the highest number of novel variants. Discussion: 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. © 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
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