The clinical significance of heterozygous E148Q variant in patients with familial Mediterranean fever.

OBJECTıVE: Our objective was to compare the clinical characteristics of heterozygous E148Q-positive familial Mediterranean fever (FMF) patients with those of E148Q/M694, M694V-homozygous, and M694V-heterozygous-positive patients.

methodsTel-Hashomer classification criteria were used to diagnose FMF. Exons 2, 3, 5, and 10 MEFV mutations were evaluated using the multiplex-PCR reverse hybridization method. The Tel-Hashomer FMF severity score was taken into consideration for FMF severity. The severity score was determined taking into account the period before using colchicine. The clinical features of FMF patients with the E148Q variant were compared to those with heterozygous E148Q plus M694V, and to patients with heterozygous or homozygous M694V mutations.

resultsThe study included 148 patients with FMF. E148Q heterozygosity was found in 14 patients (9.4%), M694V/E148Q positivity in 13 patients (8.7%), M694V heterozygosity in 49 patients (33.1%), and M694V homozygosity in 72 patients (49.6%). The disease began at an earlier age in those with M694V homozygosity compared to those with M694V heterozygosity and those with E148Q heterozygosity. However, there was no difference in disease onset age between those with M694V homozygous mutations and those with M694V/E148Q. As expected, disease severity scores, erysipelas-like erythema, and relative marriage rates were higher in those who were M694V homozygous. There was no difference between the groups in terms of fever, abdominal pain, arthritis/arthralgia, vasculitis, familial history, or frequency of ankylosing spondylitis. CONCLUSıON: Patients with heterozygous E148Q variant may exhibit main clinical features of FMF disease. Key Points • About 10% of FMF patients have heterozygot E148Q variant. • The clinical characteristics of patients with E148Q variant may be similar to those of patients with Exon 10 mutation.