Seung Shin Park1, Se Song Jang2, Chang Ho Ahn1, Jung Hee Kim1, Hye Seung Jung1, Young Min Cho1,3, Young Ah Lee4, Choong Ho Shin4,5, Jong Hee Chae4,5, Jae Hyun Kim6, Sung Hee Choi3,7, Hak C Jang3,7, Jee Cheol Bae8, Jong Cheol Won9, Sung-Hoon Kim10,11, Jong-Il Kim2,12,13, Soo Heon Kwak1, Kyong Soo Park1,3,14. 1. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 2. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea. 3. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. 4. Department of Pediatrics, Seoul National University Hospital, Seoul, Republic of Korea. 5. Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea. 6. Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. 7. Department of Internal Medicine, Seoul National University Bundang Hospital. 8. Department of Internal Medicine, Samsung Changwon Hospital, Changwon, Republic of Korea. 9. Department of Internal Medicine, Sanggye Paik Hospital, Seoul, Republic of Korea. 10. Department of Internal Medicine, Cheil General Hospital & Women's Healthcare Center, Seoul, Republic of Korea. 11. Department of Internal Medicine, Dankook University College of Medicine, Seoul, Republic of Korea. 12. Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea. 13. Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Republic of Korea. 14. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
Abstract
PURPOSE: Monogenic diabetes is a specific type of diabetes in which precision medicine could be applied. In this study, we used targeted panel sequencing to investigate pathogenic variants in Korean patients clinically suspected to have monogenic diabetes. METHODS: The eligibility criteria for inclusion were non-type 1 diabetes patients with an age of onset ≤ 30 years and a BMI (body mass index) ≤ 30 kg/m2. Among the 2,090 non-type 1 diabetes patients, 109 were suspected to have monogenic diabetes and subjected to genetic testing. We analyzed 30 monogenic diabetes genes using targeted panel sequencing. The pathogenicity of the genetic variants was evaluated according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: Among the 109 suspected monogenic diabetes patients, 23 (21.1%) patients harbored pathogenic/likely pathogenic variants. A total of 14 pathogenic/likely pathogenic variants of common maturity onset diabetes of the young (MODY) genes were identified in GCK, HNF1A, HNF4A, and HNF1B. Other pathogenic/likely pathogenic variants were identified in WFS1, INS, ABCC8 and FOXP3. The mitochondrial DNA 3243 A>G variant was identified in five participants. Patients with pathogenic/likely pathogenic variants had a significantly higher MODY probability, a lower BMI, and a lower C-peptide level than those without pathogenic/likely pathogenic variants (P=0.007, P=0.001, and P=0.012, respectively). CONCLUSIONS: Using targeted panel sequencing followed by pathogenicity evaluation, we were able to make molecular genetic diagnoses for 23 (21.1%) suspected monogenic diabetes patients. Lower BMI, higher MODY probability, and lower C-peptide levels were characteristics of these participants.
PURPOSE: Monogenic diabetes is a specific type of diabetes in which precision medicine could be applied. In this study, we used targeted panel sequencing to investigate pathogenic variants in Korean patients clinically suspected to have monogenic diabetes. METHODS: The eligibility criteria for inclusion were non-type 1 diabetespatients with an age of onset ≤ 30 years and a BMI (body mass index) ≤ 30 kg/m2. Among the 2,090 non-type 1 diabetespatients, 109 were suspected to have monogenic diabetes and subjected to genetic testing. We analyzed 30 monogenic diabetes genes using targeted panel sequencing. The pathogenicity of the genetic variants was evaluated according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: Among the 109 suspected monogenic diabetespatients, 23 (21.1%) patients harbored pathogenic/likely pathogenic variants. A total of 14 pathogenic/likely pathogenic variants of common maturity onset diabetes of the young (MODY) genes were identified in GCK, HNF1A, HNF4A, and HNF1B. Other pathogenic/likely pathogenic variants were identified in WFS1, INS, ABCC8 and FOXP3. The mitochondrial DNA 3243 A>G variant was identified in five participants. Patients with pathogenic/likely pathogenic variants had a significantly higher MODY probability, a lower BMI, and a lower C-peptide level than those without pathogenic/likely pathogenic variants (P=0.007, P=0.001, and P=0.012, respectively). CONCLUSIONS: Using targeted panel sequencing followed by pathogenicity evaluation, we were able to make molecular genetic diagnoses for 23 (21.1%) suspected monogenic diabetespatients. Lower BMI, higher MODY probability, and lower C-peptide levels were characteristics of these participants.