MVK, NLRP3, TNFRSF1A and MEFV gene mutation distributions in childhood autoinflammatory diseases: Experiences in North Anatolia

Abstract

Autoinflammatory diseases (AID) are characterised by recurrent fever and inflammation without an apparent infectious etiology and include Familial Mediteranean Fever (FMF), Tumour Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Hyper-IgD/ Mevalonate Kinase Deficiency Syndrome (HIDS/MKD), Cryopyrin-Associated Periodic Syndromes (CAPS) associated with MEFV, TNFRSF1A, MVK and NLRP3 gene variants. Totally 286 pediatric patients prediagnosed with AID were included in this study. Targeted sequence analysis of MEFV, TNFRSF1A, MVK and NLRP3 genes were performed with Sanger sequencing. Patients were grouped into two categories by the presence of MEFV variant: AIDgroup and MEFV-WTgroup.194 patients fell into AIDgroup and remaining 92 patients were in MEFV-WTgroup. Genetic variants were detected in 69% (135/194) of the patients in first group (AIDgroup). Of these patients, 62 (46%) had MEFV, 41 (30%) had MVK, 20 (15%) had NLRP3, 12 (9%) had TNFRSF1A variants. Pathogenic variants in these genes other than MEFV were detected in 6 (3%) of the 194 patients. Five of them had heterozygous variants in the MVK gene including V377I (four patients) and N205S variants (one patient). Also, in the TNFRSF1A gene N145S variant was detected in only one patient (0.5%). No pathogenic variant was detected in the NLRP3 gene. In second group (MEFV-WTgroup), 3% (3/92) of the patients had pathogenic variants including NLRP3 I313V variant (2 patients) and MVK V377I variant (1 patient). No pathogenic variant was detected in the TNFRSF1A gene. This is the first study to describe the distributions of variants in the MEFV, NLRP3, MVK and TNFRSF1A genes of the pediatric AID population in Central Black Sea region of Turkiye. Our results are consistent with the literature in terms of the variant distribution. However, pathogenic variant rates were lower than the literature data. The variant spectrum was also limited in this study possibly due to a smaller study size.