Spectrum of MEFV variants in 8,252 patients from Eastern and Southeastern Anatolia: a large single-center cohort...

Familial Mediterranean Fever (FMF) is a monogenic autoinflammatory disorder caused by variants in MEFV. Although Türkiye carries a considerable FMF burden, large contemporary single-center genetic datasets from Eastern and Southeastern Anatolia are still limited. Because the frequency and distribution of MEFV variants differ across populations and regions, locally derived reference data remain important for clinical interpretation.

To characterize the MEFV variant spectrum and genotype categories in a large single-center cohort representing Eastern and Southeastern Anatolia.

We performed a retrospective review of 8,252 consecutive referrals tested for recurrent MEFV common variants at a tertiary genetics laboratory between 2019 and 2026. Demographic variables and genotype results were retrieved from the laboratory information system. Results were grouped as wild-type (WT), monoallelic, or multi-allelic, and multi-allelic findings were further classified as homozygous, compound heterozygous, or complex multi-site configurations.

The median age was 17 years (mean 22.0 ± 16.9 years; range 0-84), and 53.8% of individuals were female. Genotype categories were distributed as follows: WT 60.4% (4,985/8,252), monoallelic 28.2% (2,327/8,252), and multi-allelic 11.4% (940/8,252), including homozygous 3.8% (311/8,252), compound heterozygous 6.9% (569/8,252), and complex multi-site 0.7% (60/8,252). The most frequent variants were M694V 14.5% (1,199/8,252), E148Q 14.0% (1,158/8,252), V726A 5.2% (426/8,252), and M680I (G > C) 4.1% (337/8,252). Exon 10 variants accounted for a substantial proportion of variant-positive findings, while E148Q was common but predominantly heterozygous. Variant rankings were broadly similar between females and males.

This study provides a large region-specific reference for MEFV variation in Eastern and Southeastern Anatolia. The predominance of M694V and other exon 10 variants, together with the high background frequency of E148Q, has direct relevance for pre-test counseling, targeted testing strategies, and interpretation of routine FMF results. Further work incorporating sequencing-based assays and standardized clinical follow-up will be necessary to refine genotype-phenotype relationships and improve variant interpretation in this high-burden setting.