Detection of genetic mutations underlying early-onset systemic lupus erythematosus.

This article focuses on the investigation of monogenic causes in pediatric patients with early-onset systemic lupus erythematosus (SLE), defined as disease onset at or before six years of age. Among 15 early-onset SLE patients studied, whole exome sequencing identified significant gene mutations in five cases (33.3%), involving DNASE1L3, ACP5, IFIH1, and C1S genes, some of which were novel variants. These mutations are linked to pathways affecting immune regulation, including complement deficiencies and type I interferonopathies, and were associated with diverse clinical manifestations such as skin involvement, nephritis, hematologic abnormalities, and skeletal dysplasia. The study highlights the importance of genetic screening in early-onset SLE for improved disease management and genetic counseling, while noting limitations including retrospective data collection and incomplete functional validation of novel variants.