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

Objective: We aimed to investigate the presence of monogenic causes of systemic lupus erythematosus (SLE) in our early-onset SLE patients.

Methods: Fifteen pediatric SLE cases who had early disease onset (≤6 years) were enrolled in this study. All patients fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria. Genomic DNA was used for whole exome sequencing (WES). Pathogenic variants were confirmed by Sanger sequencing.

Results: The median age at diagnosis of 15 early-onset SLE patients included in the study was 4 (2-6) years (F/M = 12/3). Significant gene mutations were detected in five of these patients (33.3%). Patients 1 and 2 with homozygous mutations [ and variants] had skin involvement and oral ulcers. One of them (patient 1) had arthritis and nephritis, and another (patient 2) had nonscarring alopecia and thrombocytopenia. They are currently clinically inactive but have positive serological findings. Patient 3 with homozygous pathogenic mutation [ variant] had arthritis, nephritis, short stature, and skeletal dysplasia. Patient 4 with a heterozygote novel mutation [ variant] had skin findings and leukopenia. Patient 5 with novel variant [homozygous variant] had marked skin findings, oral ulcers, nonscarring alopecia, pancytopenia, and low total hemolytic complement CH50 level. All patients have responded to the treatments and have low Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, on therapy.

Conclusion: Genetic causes should be investigated in early-onset SLE, for better management and genetic counseling. On the other hand, multicenter studies may help to further define genotype-phenotype associations.