タイの新生児糖尿病患者における全エクソームシーケンシングの標的解析

Neonatal diabetes mellitus (NDM) typically presents within the first 6 months of life and generally lacks islet autoantibodies. Genetic elucidation of NDM is a prime example of precision medicine in diabetes. However, no published genetic data exist for NDM in Thailand. We aimed to assess the genetic etiology of Thai NDM using whole exome sequencing (WES). We enrolled 14 Thai patients with NDM and measured GAD65, IA-2, and ZnT8 autoantibodies. We then performed WES and analyzed 43 NDM-related genes to identify causative variants. All subjects tested negative for the three islet autoantibodies. Eight harbored variants in well-established NDM genes (KCNJ11 [n = 5], ABCC8 [n = 1], INS [n = 2 in identical twins]). Two patients with KCNJ11 variants (rs80356616: p.Val59Met and rs8035661: p.Arg50Gln) achieved excellent glycemic control on sulfonylureas, illustrating precision therapy. The remaining six carried pathogenic variants in genes associated with monogenic diabetes, including LRBA, EIF2AK3, DOCK8, WFS1, GATA6, CISD2/SLC9B1, and COQ2. This is the first report on the genetic etiology of NDM in Thailand. WES is an effective approach to identifying variants in this rare diabetes subtype. Larger cohort studies are needed to determine the true prevalence of NDM in Thailand.