Contribution of Genetic and Environmental Risk Factors in a Juvenile Idiopathic Arthritis Large Family With SERPINA1 Gene Mutations

Abstract

Objectives Although the underlying mechanisms and mediators of arthritis in juvenile idiopathic arthritis (JIA) are not well understood, accumulated evidence supports the mixt role of genetic and environmental factors. Few reports of multiplex families with JIA were published until now. The aim of this study was to identify new genetic or environmental associations concerning the patients of a kindred with juvenile idiopathic arthritis and psoriatic features (JIAPs). Methods Here, we characterized an extended multiplex family of 5 patients with juvenile idiopathic arthritis and psoriatic features (PsA) at the clinical and genetic level, using whole exome sequencing. Results We did not confirm in our family the linkage with the genetic factors already described that might be associated with increase susceptibility to JIA. We found a carrier status of siblings who inherited a pathogenic allele of the SERPINA1 gene from their mother who herself has two heterozygous pathogenic variants in the SERPINA1 gene. Conclusions Our data showed that JIA results from pleiotropic effects of environmental background with an only minor monogenic contribution. Even that a monogenetic factor could not be proved, some genetic factor as SERPINA1 mutations which can sensitize for psoriatic arthritis development seems to be involved. Further investigation must be done to prove whether SERPINA1 mutations may have a potential JIA causality.