Ibrahim Alkhatib

Background:

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder caused by MEFV variants, with marked geographic variation in mutation patterns. Syrian molecular data remain limited, and the significance of non-exon 10 variants, particularly E148Q, remains controversial.

Methods:

We conducted a retrospective, descriptive, laboratory-based study using records from a private reference laboratory in Damascus, Syria, receiving samples nationwide. Between 2018 and 2025, 6,067 individuals underwent targeted 24-variant MEFV testing by multiplex real-time PCR. The analytic cohort included those with at least one detected variant. Genetic status was classified as monoallelic or biallelic/multiallelic. Available same-day laboratory data were summarized descriptively.

Results:

Among 6,067 individuals tested, 2,595 (42.8%) had at least one MEFV variant; 52.5% were female, and mean age was 24.75 ± 11.24 years. Overall, 57.3% were monoallelic and 42.7% were biallelic/multiallelic. Heterozygous genotypes predominated (57.3%), followed by compound/multiple (24.7%) and homozygous (18.1%) profiles. In allele-based analysis (2N = 5,190), the most frequent mutant alleles were M694V (24.07%), E148Q (18.63%), and V726A (12.54%). E148Q appeared in both isolated and exon 10–associated contexts. Inflammatory markers were descriptively higher in the biallelic/multiallelic group.

Conclusions:

This large Syrian cohort shows an MEFV variant spectrum centered on M694V, with substantial contributions from E148Q and V726A. The frequent but heterogeneous occurrence of E148Q supports cautious, exon-aware interpretation.