Comprehensive MEFV Variant Spectrum in Pediatric Patients with Suspected Familial Mediterranean Fever: A Whole-Gene Sequencing Study

Objective: To determine the Mediterranean Fever (MEFV) variant spectrum using whole-gene next-generation sequencing (NGS) in pediatric cases with suspected Familial Mediterranean Fever (FMF). Methods: This retrospective cross-sectional study included 471 pediatric cases referred for MEFV analysis. All exons were analyzed using NGS, and variants were classified according to American College of Medical Genetics and Genomics criteria. Results: At least one MEFV variant was detected in 59.4% of cases. A total of 23 variants were identified, predominantly in exon 10 (43.5%) and exon 2 (34.8%). The most frequent variants were R202Q (43.3%), E148Q (16.3%), and M694V (13.7%). A low-frequency variants of uncertain significance, G150R, was detected in one case. Heterozygous genotypes were the most common (59.6%). Conclusion: Whole-gene sequencing enables the detection of both common and rare MEFV variants that may be missed by limited mutation panels. However, frequently detected variants, such as R202Q, require careful interpretation because of their high population frequency and controversial pathogenicity.