In this study, we identified two homozygous mutations in the TREX1 gene (c.-26-1G>A and c.-26-95G>T, based on NM_033629.6) in two Inuit siblings from the Sanikiluaq region of North of Quebec, presenting with severe developmental delay, neurodegeneration, and systemic inflammation. This evidence concerns the gene TREX1 and Global developmental delay.