BACKGROUND Systemic lupus erythematosus (SLE) comprises a wide range of diverse clinical manifestations. To date, around 35 single genes are known to cause SLE/SLE like syndromes in humans. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to nonspecific presentation, different clinical manifestations in children vs. adults, high number of causative genes, and lack of clear indications for genetic testing.
METHODS We employed whole exome sequencing (WES) in 4 patients presented with childhood-onset SLE to reveal cases that can be explained by a single-gene (monogenic) mutation. All cases were sent for genetic analysis given severe and/or non-typical clinical presentation.
RESULTS Using WES we identified causative mutations in five different genes in four families in whom the index patient presented with severe form of childhood-onset SLE. We detected mutations in five known disease-causing genes: C1QC, SLC7A7, LAMAN, PTEN and DNASE1L3. None of the above monogenic syndromes were established on clinical grounds before this analysis.
CONCLUSIONS Our findings demonstrate significant detection rate for monogenic etiologies using WES and reveal broad genetic heterogeneity for childhood-onset SLE. These results highlight the importance of genetic diagnosis especially for children with severe or atypical presentation. In addition, applying WES to the diagnostic approach in childhood-onset SLE, provides opportunities for an accurate and early etiology-based diagnosis and improved clinical management.
