MEFV Gene Sequencing for Unresolved Molecular Diagnosis in Egyptian Familial Mediterranean Fever Patients; Role of R202Q Variant

Background: Familial Mediterranean fever (FMF) diagnosis depends mainly on clinical criteria. The genetic diagnosis is important especially in patients without typical clinical phenotypes. There are twelve common mutations that can be detected by reversed hybridization. This study aimed to sequence MEFV gene in clinically diagnosed FMF patients, searching for a missing variant that was assumed not to be covered by the screening panel. Materials and methods: Sanger sequencing for the whole MEFV gene 10 exons was performed in twenty patients with clinical diagnosis of FMF whose genetic screening by reversed hybridization (RH) revealed no or only one heterozygous variant. Results: Various variants were detected except for exons 7 and 8. The most frequent variants detected were G138G (n = 10), A165A (n = 8) & R202Q (n = 5) in exon 2; R314R (n = 12) in exon 3; c.1356 + 44A > G (n = 12) in exon 4; D510D (n = 18), Q476Q (n = 18) & E474E (n = 18) in exon 5 and c.1610 + 96C > T (n = 15) & c.1588-69 G > A (n = 14) in exon 6. R202Q was detected in 3 patients (15%) in homozygous form and in 2 patients (10%) in heterozygous form. The genotypic-phenotypic correlation showed no statistically significant correlation except between R202Q variant with the disease severity (p = 0.037), the A165A variant with family history (p = 0.036), the E148Q and A448A variants with erysipelas like erythema (ELE) (p = 0.042 in both). Conclusion: MEFV gene sequencing may be useful for continuous addition of knowledge on the variants, their clinical context and patients' prognosis. Being of high rate of occurrence, the R202Q should be further investigated in different populations and on a wider scale among Egyptian population as it may be a disease-causing variant.