EVALUATION OF GENETIC TESTING IN ADULT PATIENTS WITH SUSPECTED SYSTEMIC AUTOINFLAMMATORY DISORDERS

Objective: This study aimed to compare the clinical features of patients with suspected systemic autoinflammatory diseases (SAIDs) by genetic status to identify the characteristics of variant-negative patients.Materials and Methods: Clinical findings and results of the targeted next-generation sequencing of “fever panel genes” of patients with suspected SAIDs were retrospectively reviewed using their medical records.Results: Records of 137 patients (79 females, 58 males, mean age 40.8±12.6) referred to our clinic between April 2019 and January 2023 were evaluated. Variants associated with the relevant phenotypes were identified in 105 patients (76.6%), whereas 32 (23.4%) had no pathogenic or likely pathogenic variants, nor variants of uncertain significance (VUS). Variant-negative patients were older at diagnosis than variant-positive ones (38.2±13.6 vs. 28.4±14.8 years; p=0.02). Fever and arthritis occurred with a similar frequency between the groups. Compared with the variant-positive patients, the variant-negative group more often presented with nausea, weight loss, diarrhoea, erythema nodosum, headache, and sensorineural hearing loss (SNHL). Cerebrovascular occlusion occurred more frequently among variant-positive patients.Conclusion: Our study illustrates that the yield of genetic screening is expected to be low in patients older than 40 years and those presenting with nausea, weight loss, diarrhoea, erythema nodosum, headache, and SNHL. A better definition of those variant-negative patients may identify some subgroups of patients with SAID features associated with potential multifactorial causes or somatic mosaic variants.