Clinical evaluation of R202Q alteration of MEFV genes in Turkish children

Abstract

To date, over 200 alterations have been reported in Mediterranean fever (MEFV) genes, but it is not clear whether all these alterations are disease-causing mutations. This study aims to evaluate the clinical features of the children with R202Q alteration. The medical records of children with R202Q alteration were reviewed retrospectively. A total of 225 children, with 113 males, were included. Fifty-five patients were heterozygous, 30 patients were homozygous for R202Q, and 140 patients were compound heterozygous. Classical familial Mediterranean fever (FMF) phenotype was present in 113 patients: 2 heterozygous and 7 homozygous R202Q, 46 double 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 % and erysipelas-like erythema in 13.3 %. 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 %, p = 0.05). R202Q alteration of the MEFV gene leads to symptoms consistent with FMF in some cases. This alteration may be associated with a mild phenotype and shows phenotypic differences other than the common MEFV mutations.

Severe liver involvement in two patients with long-term history of fever: remember familial Mediterranean fever

“…To date, FMF phenotype has been linked, by several groups, with R202Q alteration 5 6 13 14. The presence of R202Q homozygosity in both of our FMF patients is in parallel with previous findings from our group where almost 10% of Greek FMF patients carry only this mutation, which is extremely rare in the healthy Greek population 5 6.…”

The spectrum of MEFV gene mutations and genotypes in Van province, the eastern region of Turkey, and report of a novel mutation (R361T)

“…R202Q was first identified by Bernot and colleagues and has been described as a benign polymorphism (Bernot et al, 1998). Besides, R202Q (c.605GNA) was described as a frequent polymorphism, and the G allele was found to be in linkage disequilibrium (LD) with M694V in Infevers Database (Touitou et al, 2004 (Giaglis et al, 2007;Yigit et al, 2012;Comak et al, 2014). The clinical significance of the R202Q alteration in Turkish pediatric patients has been published in a paper.…”

“…R202Q in the MEFV gene has been reported to lead to symptoms consistent with the clinical findings of FMF in some patients, and the author suggested that the R202Q alteration was probably a mutation rather than a polymorphism, but it might be associated with a mild phenotype and could show phenotypic differences similar to the common MEFV mutations. Moreover, it has been suggested that patients with homozygous R202Q alteration (or R202Q with another MEFV mutation) may require colchicine treatment (Comak et al, 2014). In addition, Yigit et al reported a high association between the MEFV gene R202Q polymorphism and FMF.…”

Febrile seizures in children with familial Mediterranean fever: Coincidence or association?

“…1 Besides, exon 2 mutations including E148Q and R202Q have been reported to be associated with the mildest disease with least penetrance. 22,23 A recent study that were carried out on 104 febrile seizure patients by Ozen et al reported that MEFV gene mutations, especially M694V mutation, are positively associated with febrile seizures. 24 In the same study they also showed that of the 104 patients 68 of them were heterozygotes for any mutation and 10 patients were compound heterozygotes (4 patients for E148Q/ M694V and 6 patients for M694V/V726A).…”