Identification of genetic variants associated with monogenic autoinflammatory diseases in patients with Still's...

In this study, we aimed to identify potential variants associated with monogenic autoinflammatory diseases (AIDs) in patients with Still's disease (SD), thereby enhancing our understanding of the complex genetic mechanisms driving SD. This study included adult patients with SD who had available genetic data. Demographic characteristics, clinical findings, and laboratory test results were recorded. Genomic variants related to AIDs were detected using next-generation sequencing with a targeted gene panel for all coding exons and exon-intron boundaries of relevant genes. Identified variants were interpreted using multiple in silico prediction models and genomic databases and classified following the 2015 ACMG/AMP recommendations. Thirty-nine patients were included, of whom 19 (49%) carried at least one genetic variant. A total of 22 distinct variants were identified across 15 genes, including NLRP1, NLRP3, NLRP12, MEFV, LPIN2, IFIH1, PSMB8, IL10RA, IL10RB, IL36RN, SLC29A3, PLCG2, NOD2, CARD14, and SH3BP2. All variants were monoallelic; most were missense, whereas two were frameshift variants in IFIH1 and NLRP1. Most variants were classified as variants of uncertain significance, while variants in MEFV and IFIH1 were classified as pathogenic and likely pathogenic, respectively. Different genetic variants can be observed in patients with SD, and these variants are possibly epiphenomena rather than being Still's disease-driven mutations. Their presence may contribute to variability in clinical findings and disease course, which requires further investigation to be fully understood.