High prevalence of rare FBLIM1 gene variants in an Italian cohort of patients with Chronic Non-bacterial Osteomyelitis (CNO)

Background: FBLIM1gene has been recently demonstrated to be involved in the pathogenesis of bone sterile inflammation. The aim of the study is to evaluate the prevalence ofFBLIM1gene variants in a cohort of 80 Italian patients with Chronic Non-bacterial Osteomyelitis (CNO). Methods: The coding regions ofFBLIM1gene were sequenced in a cohort of 80 patients with CNO using DNA extracted from blood lymphocytes, and PCR products were sequenced. Only rare (global MAF < 2%), coding variants detected were considered. Clinical evaluation of patients with rare variants and those without was performed. Fisher's exact test was used to compare categorical and ordinal data, and Student's t-test was used to analyze continuous data. Results: Eighteen out of 80 patients (similar to 22%) presented at least one rare coding variant inFBLIM1. Eight patients presented a variant never associated before with CNO. All patients presented classical features of CNO and no statistical difference between patients with presence ofFBLMI1variants and those without were found in terms of clinical manifestation, treatment, and outcome. Conclusion: Considering the high frequency of rare variants in our CNO cohort, our data seem to confirm a possible role ofFBLIM1in the pathogenesis of CNO suggesting that CNO is a disorder of chronic inflammation and imbalanced bone remodeling.