Identification of rare genetic variants in Juvenile Idiopathic Arthritis using whole exome sequencing

Introduction Juvenile Idiopathic Arthritis (JIA) is the most common form of chronic arthritis in children. JIA is characterized by onset of disease before the age of 16, with arthritis lasting >6 weeks, and with an unknown cause. Among JIA, seven sub-groups based on clinical and biological features have been individualized namely: systemic arthritis (sJIA) with autoinflammatory conditions, persistent and extended oligoarthritis (per-oJIA and ext-oJIA, respectively), rheumatoid factor-positive polyarthritis (RFpos-pJIA), enthesitis-related arthritis (ERA), psoriatic arthritis (PsA), and undifferentiated arthritis. Physiopathology of JIA is complex and JIA is considered to be a multifactorial disease due to the combination of genetic and environmental factors. Searching for genetic factors in JIA during the last decade, the introduction of genome-wide association studies (GWAS) and wholeexome sequencing have discovered several new loci associated with JIA susceptibility and have identified the disease-associated gene monogenic form of sJIA, respectively. However, despite these novel knowledge, our understanding of JIA pathogenesis still remains poorly elusive and accumulating evidence supports genetic variability as playing a key role in JIA development.