MEFV gene mutations in Henoch- Schonlein purpura

ensari, arzu/0000-0001-7036-4457WOS: 000334521000017PubMed: 23981758AimCoexistence of familial Mediterranean fever (FMF) with various systemic vasculitides, including Henoch-Schonlein purpura (HSP) and other inflammatory disorders has been reported and the MEFV gene has been suggested to play an important role in the pathogenesis of this association. In the present study, the mutation rate of the MEFV gene in HSP and its association with the clinical course of the disease were evaluated. MethodThe study group comprised 68 children (36 boys and 32 girls) diagnosed as having HSP. The spectrum and degree of organ involvement and the levels of serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were documented for each patient. Allele-specific PCR using oligonucleotide probes which include 12 MEFV mutations (E148Q, P369S, F479L, M680I [G/C], M680I [G/A], I692del, M694V, M694I, K695R, V726A, A744S, R761H) were used for mutation analysis. ResultsOf the 68 patients studied, 50 (74%) showed no mutation, while 18 (26%) had MEFV mutation. Mutation analysis of the whole group revealed that 15 (22%) patients were heterozygous for one of the screened MEFV mutations, while three (4.5%) patients were compound heterozygous for two of the studied mutations, and one (1.5%) patient was homozygous for E148Q/E148Q mutations. Gastrointestinal and joint involvement, and edema were more frequently observed in patients with MEFV mutations, while ESR and CRP levels were significantly higher (P<0.05) in patients with MEFV mutations. ConclusionMEFV mutations, especially, E148Q and M694V, mutations might be associated with HSP and may affect clinical presentation and laboratory findings in HSP patients

The frequency of Familial Mediterranean fever gene mutations and genotypes at Kirikkale and comparison with the mean of regional MEFV mutation frequency of Turkey

WOS: 000332000400025PubMed: 24381109In this study we have retrospectively analysed the mutation spectrum of the 351 Familial Mediterranean fever patients referred to KA +/- rA +/- kkale University Faculty of Medicine, Department of Medical Genetics Laboratory over a period of 5 years and compared them with Turkey's mean. We have found 11 different mutations, including rare mutations such as F479L, K695R, M680I(G/A) and 45 different genotypes showing the heterogeneity of MEFV mutations in Central Anatolia. The most three prevalent mutations were M694V (14.8 %), E148Q (7.1 %) and M680I(G/C) (4.1 %) in accordance with the literature. We have also investigated R202Q in our routine molecular diagnosis. Mutation causing R202Q (c.605G > A) change was described as a frequent polymorphism and G allele was found in linkage disequilibrium (LD) with M694V. There are limited number of studies investigating R202Q, some of them implicate that its homozygote state is disease causing. We showed the high frequency of R202Q (23.7 %) with and without M694V in all the groups analysed and its high LD rate with M694V in the diagnosed group. Our study is reflecting the mutational heterogeneity of MEFV and summarize mutational spectrum of Turkey's geographical regions and overall Turkey

The spectrum of FMF mutations and genotypes in the referrals to molecular genetic laboratory at K&Aumlaut +/- r&Aumlaut +/- kkale University in Turkey

WOS: 000263798400019PubMed: 18389382Familial Mediterranean Fever (FMF) is an autosomal recessive genetic disorder characterised by recurrent and self-limited abdominal pain, synovitis and pleuritis. MEFV gene mutations are responsible from the disease and its protein product, pyrin or marenostrin, plays an essential role in the regulation of the inflammatory reactions. MEFV gene contains 10 exons and most of the mutations have been found on the last exon. Up to date, 152 mutations and polymorpisms have been reported inwhere V726A, M694V, M694I, M680I and E148Q are the most common mutations. In this study, MEFV allele frequencies of 136 individuals (60 from Pediatry, 76 from Internal Medicine) have been evaluated, and compared with each other. Asymptomatic individuals with FMF family history (4 from Pediatry, 6 from Internal Medicine) were excluded from the analysis. The prominent mutations indicated in the Pediatry group are V726A, M694V and M680I (G/C) and with the allele frequency of 0.06, 0.05 and 0.04 respectively while they were E148Q, M694V, M680I (G/C) in the Internal Medicine group with the allele frequency of 0.12, 0.08 and 0.04. The E148Q mutation is significantly overrepresented in the adult referrals (P = 0.02). Mutation on both alleles was observed in only 12% of cases. Overall mutation frequency was low, seen in 26.2% (66/252). However, when only diagnosed patients were analyzed it is 72.7% (16/22). It is also interesting that 63% of individuals are female that there may be sex influence on FMF phenotype