Background Familial Mediterranean Fever (FMF) is an inherited autosomal recessive disorder, caused by mutations in MEditerraneanFeVer gene (MEFV). To date over 200 alterations have been reported in MEFV genes. But, it is not clear whether all these alterations are disease-causing mutations.
Objectives To evaluate the clinical and laboratory features of the children with R202Q alteration.
Methods In our institution, molecular diagnosis of FMF was based on the automated DNA sequencing of the mutations in exon 2 and exon 10 of MEFV gene. Before December 2012, R202Q (605G>A) mutations were not reported to the clinicians, because it was not considered as a disease causing mutation. As recently some authors suggest that R202Q may be a disease causing mutation for FMF, MEFV mutation analysis that was performed between February 2009 and December 2012 were re-evaluted for R202Q alterations. Patients with heterozygous R202Q, homozygous R202Q and compound heterozygous and complex cases were included in the study. Their medical records were screened retrospectively.
Results A total of 225 children, 113 males, were included. The patients were classified according to the MEFV mutation types: heterozygous R202Q in 55, homozygous R202Q in 30 and compound heterozygous and complex cases in 140. Also, patients were re-classified according to FMF phenotypes as phenotype 1 in 113 (50.2%), phenotype 3 in 7 (3.1%) and “FMF-like” disease in 105 (46.6%). None of the patients were diagnosed as FMF phenotype 2. In FMF groups (phenotype 1), a total of 113 patients had R202Q alteration: 2 heterozygous and 7 homozygous R202Q, 46 homozygous R202Q and M694V, and 58 compound heterozygous. The main clinical characteristics of the patients were: abdominal pain in 71.5%, fever in 37.7%, arthralgia/myalgia in 30.2%, arthritis in 10.2%, chest pain in 14.6%, erysipelas-like erythema in 13.3%, headache in 6.2% and history of appendectomy in 6.2%. The frequency of abdominal pain was significantly lower in patients with homozygous R202Q alteration (p=0.021), whereas patients with heterozygous R202Q mutations, though not statistically significant, had a higher frequency of arthralgia/myalgia (40.0%).
Conclusions R202Q alteration of MEFV gene leads to symptoms consistent with FMF in some cases. This alteration may be associated with a mild phenotype and show phenotypic differences other than the common MEFV mutations.
Disclosure of Interest None declared