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Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by insulin deficiency and loss of pancreatic islet β-cells. The objective of this study is to identify de novo mutations in 13 trios from singleton families that contribute to the genetic basis of T1DM through the application of whole-exome sequencing (WES). Of the 13 families sampled for this project, 12 had de novo variants, with Family 7 having the highest number (nine) of variants linked to T1DM/autoimmune pathways, whilst Family 4 did not have any variants past the filtering steps. There were 10 variants of 7 genes reportedly associated with T1DM (<i>MST1; TDG; TYRO3; IFIHI; GLIS3; VEGFA; TYK2</i>). There were 20 variants of 13 genes that were linked to endocrine, metabolic, or autoimmune diseases. Our findings demonstrate that trio-based WES is a powerful approach for identifying new candidate genes for the pathogenesis of T1D. Genotyping and functional annotation of the discovered de novo variants in a large cohort is recommended to ascertain their association with disease pathogenesis.