Results of molecular genetic testing in 115 patients with suspected monogenic autoinflammatory disease

In the last decade, an interest has increased in autoinflammatory diseases (AIDs) associated with a mutation in a specific gene, while the pathogenetic significance of the identified genetic variants continues to be clarified.
Objective: to study the frequency and spectrum of genetic variants identified by molecular genetic testing (MGT) and the clinical features in patients with suspected monogenic AIDs (mAIDs).
Material and methods. MGT of target genes was performed in 115 patients with suspected mAIDs (median age 10 [5; 14] years; male-to-female ratio 1:1.1) using massively parallel sequencing (in 89% of cases, a 65-gene panel was used).
Results and discussion. The patients were divided into two groups. Group 1 included 44 (38%) patients with identified genetic variants, and Group 2 included 71 patients with genetically negative MGT results. Thirty-six monogenic variants were identified (11 in the MEFV gene, 5 in NOD2, 4 in NLRP3, 3 in TNFRSF1A, 2 each in MVK, RAG1, NLRP1, ADA2, and 1 each in IFIH1, NLRP12, UNC13D, RIPK1, IL36RN), as well as 8 digenic/oligogenic combinations (2 in MEFV/TNFRSF1A; 1 each in MEFV/MVK/TNFAIP3, MEFV/NOD2/PSTPIP1, NOD2/MEFV, IL36RN/STX11, MEFV/NLRP12, SH2D1A/TNFAIP3). In both groups, the most common were: fever (in 89% and 88% of cases), skin involvement (59% and 47%), arthralgia (61% and 45%), arthritis (36% and 25%), gastrointestinal symptoms (34% and 37%), and lymphadenopathy (28% and 35%), hyperproduction of autoantibodies was detected in 15% and 27% of cases, respectively. Differences between the groups for these parameters were not statistically significant. Chest pain was observed significantly more often in Group 1 than in Group 2 (14% vs 1%, respectively; p=0.008).
Conclusion. MGT identified mutations in 38% of patients with suspected mAIDs. Genetic variants from the group of major monogenic AIDs (FMF, TRAPS, CAPS, HIDS/MKD) were most common. When clinical and laboratory data were compared between the groups with positive and negative MGT results, no substantial differences were found. Patients with negative MGT results who meet AIDs criteria require extended evaluation, including whole-exome/whole-genome sequencing.

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