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Identifying Pathogenic Variants of Monogenic Diabetes Using Targeted Panel Sequencing in an East Asian Population

2019; Oxford University Press; Volume: 104; Issue: 9 Linguagem: Inglês

10.1210/jc.2018-02397

1945-7197

Seung Shin Park, Se Song Jang, Chang Ho Ahn, Jung Hee Kim, Hye Seung Jung, Young Min Cho, Young Ah Lee, Choong Ho Shin, Jong‐Hee Chae, Jae Hyun Kim, Sung Hee Choi, Hak Chul Jang, Jee Cheol Bae, Jong Cheol Won, Sung‐Hoon Kim, Jong‐Il Kim, Soo Heon Kwak, Kyong Soo Park,

Genomics and Rare Diseases

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 with clinically suspected monogenic diabetes.The eligibility criteria for inclusion were patients with nontype 1 diabetes with age at onset ≤30 years and body mass index (BMI) ≤30 kg/m2. Among the 2090 patients with nontype 1 diabetes, 109 had suspected monogenic diabetes and underwent 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 Association for Molecular Pathology guidelines.Among the 109 patients with suspected monogenic diabetes, 23 patients (21.1%) 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 3243A>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).Using targeted panel sequencing followed by pathogenicity evaluation, we were able to make molecular genetic diagnoses for 23 patients (21.1%) with suspected monogenic diabetes. Lower BMI, higher MODY probability, and lower C-peptide level were characteristics of these participants.