Journal of Interdisciplinary Genomics

유전의학융합회 (Interdisciplinary Society of Genetic & Genomic Medicine)
권호 표지
DOI QR코드

DOI QR Code

Targeted Panel Exome Sequencing in Suspected Monogenic Diabetes: Single-Center Pilot Study

  • Lee, Sangwoo (Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital) ;
  • Lee, Gi Min (Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital) ;
  • Lee, MiSeon (Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital) ;
  • Lee, Rosie (Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital) ;
  • Moon, Jung Eun (Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital)
  • 투고 : 2022.03.11
  • 심사 : 2022.04.11
  • 발행 : 2022.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Purpose:Maturity onset diabetes of the young (MODY) is the most common hereditary form of diabetes mellitus (DM), with similar clinical manifestations to type 1 or type 2 DM, leading to diagnostic ambiguity. Despite increased genetic research on monogenic DM, studies with Asian populations are limited. Therefore, we investigated mutation in possible monogenic DM and MODY in Korean children and aldolescents. Methods: Targeted panel exome sequencing including 32 targets genes was performed for 41 patients with suspected monogenic DM at Kyungpook National University Children's Hospital. Results: Variants were detected in 19 patients, including those in known MODY-associated genes (HNF4A, GCK, HNF1A, CEL, PAX4, INS, and BLK) and monogenic DM-associated genes (WFS1, FRX6, and GLIS3). Conclusion: MODY variants were detected more than expected. Targeted exon sequencing is helpful in diagnosing MODY or possible monogenic DM patients.

키워드

참고문헌

  1. Joslin EP, Kahn CR. Joslin's Diabetes Mellitus. Lippincott Williams & Wilkins. 2005
  2. Badiu C, Williams textbook of endocrinology. Acta Endocrinologica (Bucharest) 2019;15:416 https://doi.org/10.4183/aeb.2019.416
  3. Fajans SS, Bell GI, Polonsky KS. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. New England Journal of Medicine 2001;345:971-80. https://doi.org/10.1056/NEJMra002168
  4. Brunerova L, Rahelic D, Ceriello A, Broz J. Use of oral antidiabetic drugs in the treatment of maturity-onset diabetes of the young: A mini review. Diabetes/metabolism Research and Reviews 2018;34:e2940. https://doi.org/10.1002/dmrr.2940
  5. Shepherd MH, Shields BM, Hudson M, Pearson ER, Hyde C, Ellard S, et al. A UK nationwide prospective study of treatment change in MODY: genetic subtype and clinical characteristics predict optimal glycaemic control after discontinuing insulin and metformin. Diabetologia 2018;61:2520-7. https://doi.org/10.1007/s00125-018-4728-6
  6. Oliveira SC, Neves JS, Perez A, Carvalho D. Maturity-onset diabetes of the young: From a molecular basis perspective toward the clinical phenotype and proper management. Endocrinologia, Diabetes y Nutricion 2020;67:137-47. https://doi.org/10.1016/j.endinu.2019.07.012
  7. Firdous P, Nissar K, Ali S, Ganai BA, Shabir U, Hassan T, et al. Genetic testing of aturity-onset diabetes of the young current status and future perspectives. Frontiers in Endocrinology 2018;9:253. https://doi.org/10.3389/fendo.2018.00253
  8. Anik A, Catli G, Abaci A, Bober E. Maturity-onset diabetes of the young (MODY): an update. Journal of Pediatric Endocrinology and Metabolism 2015;28:251-63. https://doi.org/10.1515/jpem-2014-0384
  9. Kim JH. Diagnosis and glycemic control of type 1 diabetes. The Journal of Korean Diabetes 2015;16:101-7. https://doi.org/10.4093/jkd.2015.16.2.101
  10. Kim SH. Maturity-onset diabetes of the young: what do clinicians need to know?. Diabetes & Metabolism Journal 2015;39: 468-77. https://doi.org/10.4093/dmj.2015.39.6.468
  11. Park SS, Jang SS, Ahn CH, Kim JH, Jung HS, Cho YM, et al. Identifying pathogenic variants of monogenic diabetes using targeted panel sequencing in an east Asian population. The Journal of Clinical Endocrinology & Metabolism 2019;104:4188-98. https://doi.org/10.1210/jc.2018-02397
  12. Johnson SR, Ellis JJ, Leo PJ, Anderson LK, Ganti U, Harris JE, et al. Comprehensive genetic screening: The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort. Pediatric Diabetes 2019;20:57-64. https://doi.org/10.1111/pedi.12766
  13. Yang YS, Sohn TS. Age at Diagnosis and the Risk of Diabetic Nephropathy in Young Patients with Type 1 Diabetes Mellitus. Diabetes & Metabolism Journal 2021;45:277-8. https://doi.org/10.4093/dmj.2021.0028
  14. Torsvik J, Johansson S, Johansen A, Ek J, Minton J, Raeder H, et al. Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of monogenic diabetes. Human Genetics 2010;127:55-64. https://doi.org/10.1007/s00439-009-0740-8