Common MEFV Gene Mutations Research Articles

Increasing Importance of Genotype–Phenotype Correlations Associated with Common and Rare MEFV Gene Mutations in FMF Patients in the Last Thirty Years

Background/Objectives: Studies have shown that some mutations, especially M694V, are correlated with renal RI and/or AA. There are limited data about rare mutations on severity of the disease and RI. Today, evaluating genotype–phenotype correlations in rare mutations is important to better understand FMF. We aimed to evaluate clinical, demographic and genetic changes and genotype–phenotype correlations in pediatric patients with FMF over thirty years as well as the importance of the rare mutations. Methods: A total of 2765 pediatric patients with FMF were included in this study. Genetic results were firstly divided into ten groups including rare mutations. Rare mutations were seen in 2% of all patients and divided into eight groups. Results: There was a significant increase in compound heterozygous mutations, E148Q het/hom, R202Q het/hom, complex mutations and rare mutations in the last decade. RI wo AA was 5.8% and AA was 1% in the patients with rare mutations. While M694V and compound het with M694V were positively correlated with severe PRAS, E148Q and V726A were negatively correlated with severe PRAS (p < 0.05, R = 0.137, R = −0.077, R= −0.05, respectively). Although K695R mutation was negatively correlated with severe PRAS (p < 0.05, R = −0.04), the rate of RI was 20%. Although the rare mutation R761H was negatively correlated with severe PRAS (p < 0.05, R = −0.051), the colchicine resistance rate was 8.3%. Conclusions: It may be misleading for clinicians that mutations which have increased in frequency over the years are clinically mild. RI and AA rates in rare mutations are not less than the related rates in common mutations.

The increased chromosomal DNA damage in patients with Familial Mediterranean Fever

ABSTRACT Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disease. In this study, we aimed to assess chromosomal DNA damage and cell proliferation by using cytokinesis-block micronucleus cytome (CBMN-cyt) assay in the peripheral blood lymphocytes of untreated FMF patients carrying M694V and R202Q mutations, which are the most common MEFV gene mutations in Turkish society. The study included 20 untreated FMF patients with M694V and R202Q mutations and 20 healthy individuals of similar age and sex as the control group. Micronucleus (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) were scored in the obtained bi-nucleated (BN) cells. Additionally, the nuclear division index (NDI) was calculated using the scores of mononuclear, binuclear, and multinuclear cells. We found that MN and NPBs frequencies in FMF patients were significantly higher than in controls, and number of metaphases was significantly lower (respectively, p < 0.05, p < 0.01, and p < 0.01). However, there was no significant difference in NBUDs frequencies and NDI values between FMF patients and controls (p > 0.05). Our study is the first to evaluate FMF patients’ lymphocytes using the CBMN-cyt assay, as no previous research has been found in this respect. Increased MN and NPB frequencies may be useful as biomarkers for chromosomal DNA damage, and may indicate a potential for elevated cancer risk in untreated FMF patients.

Molecular analyses of MEFV gene mutation variants in Turkish population.

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease primarily affecting individuals of Turkish, Armenian, Arab, and non-Ashkenazi Jewish descent, caused by mutations in the MEFV gene. The aim of this study was to review the common genotype distributions of MEFV variants and mutations in the Turkish population and evaluate rare mutations. The study included 2984 patients who applied to Ankara University Ibni Sina Hospital Immunology Laboratory with clinical suspicion of FMF between 2004 and 2014. The data of patients from different regions of the country who were followed up in the immunology-rheumatology clinic with clinical suspicion and presumptive diagnosis of FMF were evaluated retrospectively. Patients were tested for all mutations in Exon 2 and Exon 10, including M694V, M680I, M694I, V726A, E148Q and R202Q. There were 2504 patients with FMF variant. According to genotyping, R202Q (n = 1567, 39.2%) was the most common mutation. The most common co-variant was the R202Q/M694V genotype (n = 507, 16.98%). Allele frequencies for MEFV mutations were as follows: R202Q (n = 1567, 39.2%), M694V (n = 1004, 25.1%), E148Q (n = 463, 11.5%), M680I (n = 354, 8.8%), V726A (n = 319, 7.9%), A744S (n = 51, 1.2%), R761H (N = 41, 1.0%), P706P (N = 25, 0.6%), E167D (N = 23, 0.5%), M694I (N = 23, 0.5%), and K695R (N = 20, 0.5%). This research revealed the prevalence of both common and rare MEFV gene mutations in Turkish FMF patients in various age groups. R202Q was the most prevalent mutation.

Articular manifestations in Egyptian children with familial Mediterranean fever

BackgroundFamilial Mediterranean fever (FMF) is an autosomal recessive auto-inflammatory disease. Arthritis in early-onset FMF is a common finding. The aim of this study was to assess frequency of arthritis in 200 Egyptian children with FMF and also to detect its clinical characteristics, response to colchicine treatment, its effect on disease severity, and the most common MEFV gene mutations in patients with arthritis.ResultsWe studied 200 children with FMF. We analyzed joint involvement in FMF attacks regarding its clinical characteristics, its effect on the disease severity, and response to colchicine treatment. We found arthritis in 20.5% of the studied population. Most of the children with arthritis had mono-articularjoint involvement during the FMF attack (73.1%), followed by oligo-articularjoint (22%). The knees and ankles were the most commonly affected joints. Arthritis was the presenting symptom in only 4%. We observed redness of the affected joints in 70.7%, and persistence of swelling after the attacks only in 17.1%. The majority of patients (85.4%) had a 75–100% decrease in the frequency of arthritic attacks after colchicine treatment. We did not find any joint disability in all studied patients, and arthritis was only present during attacks. The most frequent MEFV gene mutations in arthritic patients wereV726A and E148Q, each occurring in 28.6%. We observed an earlier age of disease onset and a more disease severity in patients with arthritis (p = 0.031 and p ≤ 0.001, respectively). We also observed that chest pain, erysipelas-like-erythema, and testicular affection were more observed in patients with arthritis (p values 0.001, 0.001, and 0.006, respectively).ConclusionThis study showed that around 20% of Egyptian children with FMF can develop arthritis during the attacks, which usually runs a benign course. The presence of arthritis can denote a more severe disease course.

The Prevalence of Three Common MEFV Gene Mutations in West Bank Population among Students of Najah National University, Palestine

Background: Familial Mediterranean fever (FMF) is an autosomal recessive disorder. The clinical symptoms of FMF are nonspecific and difficult to distinguish from similar symptoms arising from completely different diseases. Following the cloning of the gene associated with this disease (MEFV), genetic analysis of its mutations has become available. Of these mutations, five account for more than 70% of FMF cases which are; V726A, M694V, M694I, M680I and E148Q. In this study, three out of the five common mutations of MEFV gene were analyzed in apparently healthy people in West Bank, Palestine. Method: We performed A cross sectional, non-interventional, descriptive study that aims to calculate the prevalence of three common MEFV gene mutations (M694V, M680I and V726A) in the West Bank population by taking a representative sample among An-Najah National University (NNU) students at the period between November 2013- January 2014. The research included a simple questionnaire and blood sampling searching for 3 common MEFV gene mutations. DNA was extracted promptly using Phenol-Chloroform Isoamyl Alcohol (P-CIA) protocol. PCR methods were used to analyze the M694V, M680I and V726A mutations that have been previously defined by us to be three out of five commonest mutations worldwide. Results: Overall, the prevalence of three common MEFV gene mutations in West Bank population among students of NNU was 23.5 %. The most common mutation was V726A (12.7%), followed by M680I (8.3%), while the least one was M694V (2.4%). Conclusions: In conclusion, the prevalence of the MEFV gene mutations was high and similar to neighbor countries such as Syria and Iran. According to these results, genetic counseling can play important role in reducing the number of affected patients, genetic screening in families with affected patients can reduce the risk of developing complications, as amyloidosis, by providing proper prophylactic with colchicine.

MEFV mutation carriage as possible predisposition factor for the development of Post Pericardiotomy Syndrome (PPS)

Methods 86 patients who underwent cardiac surgery were studied, 45 of whom developed PPS (study group) and 41 have not (control group). Demographic data (gender, age, region of residence, ethnic origin) and type of surgery were collected. The severity of PPS was evaluated, based on a predefined scale. Genetic analysis determining carriage of one of the three most common MEFV gene mutations (M694V, V726A, E148Q) was performed.

Common MEFV Mutations in Palestinian Patients with Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is an autosomal recessive inflammatory disorder caused by mutations in the MEFV gene that encodes the pyrin protein. The disease is relatively common among people originating from the Mediterranean areas. The aim of this study was to determine the common MEFV gene mutations in 270 Palestinian patients diagnosed with FMF. The patients were screened for four common MEFV gene mutations namely, p.M694V, p.M694I, p.V726A, and p.E148Q using allele-specific polymerase chain reaction (AS-PCR). The results revealed that around 22% of the patients harbored two MEFV mutations, with the compound heterozygous forms being more prevalent than the homozygous ones. The most frequently encountered mutant allele was p.M694V which existed in around 12% of the tested chromosomes. The p.M694I, p.V226A and p.E148Q mutations were observed in around 9, 9 and 7% of the tested chromosomes, respectively. In about 29% of the patients only one mutant allele could be detected and around 49% of the patients did not show any of the investigated mutations. In conclusion, the four tested MEFV gene mutations have a significant contribution to FMF in the Palestinian population of Gaza strip. Screening for those mutations should be offered to FMF patients to confirm diagnosis and effect timely treatment. Further mutations analysis the MEFV gene should be conducted in this population in order to document additional MEFV mutations.

Familial Mediterranean Fever in Iran: A Report from FMF Registration Center.

Background. Familial Mediterranean fever (FMF) is a periodic AR autoinflammatory disorder. This comprehensive study describes FMF in Iran as a country near Mediterranean area. Materials and Methods. From the country FMF registration center 403 patients according to Tel-Hashomer criteria enrolled this study, 239 patients had MEFV gene mutations analyses. Data, if needed, was analyzed by SPSS v20. Results. 175 patients (43.4%) were female and 228 patients (56.6%) were male. The mean age was 21.3 years. Abdominal pain was in 93.3% patients and 88.1% had fever. Abdominal pain was the main complaint of patients in (49.6%). The mean interval between attacks was 36.5 ± 29.6 days and the mean duration of every episodes was 43.3 ± 34.5 hours. 15.1% of patients had positive family history and 12.7% had previous surgery; in 52.3% of patients delay in diagnosis was more than three years. 12 common MEFV gene mutations were analyzed, 21.33% were without mutations, 39.7% had compound heterozygote, 25.52% showed heterozygous, and 13.38% showed homozygous results. The most common compound genotype was M694V-V726A (% 10.46) and in alleles M694V (% 20.9) and V726A (% 12.7) were the most frequent mutations, respectively. Conclusion. M694V was the most common mutation, and the most common compound genotype was M694V-V726A. Our genotype results are similar to Arabs and in some way to Armenians, erysipelas-like skin lesions are not common in this area, and clinical criteria are the preferred methods in diagnosis of FMF.

Frequencies of the Common MEFV Gene Mutations in Adiyaman, Southeast Anatolia, Turkey.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by fever and serosal inflammation. The reasons for the disorder are mutations in the Mediterranean fever (MEFV) gene; the most common of which are M694V, M680I, M694I and V726A. In this study, we aimed to screen these common mutations of the MEFV gene and then determine the prevalence of FMF according to these mutations in Adıyaman, Southeast Anatolia, Turkey. Seven hundred and sixty-seven healthy individuals from the region of Adıyaman participated in the study. Polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) methods were used to determine the common mutations of the MEFV gene. Twenty-six (3.9%) individuals had only one mutation in the MEFV gene, 25 individuals were heterozygous and one person was homozygous for the V726A mutation (0.15%). In the present study, the V726A mutation (50.0%) was the most frequent, followed by M694V (38.5%), M680I (7.7%) and M694I (3.8%). It was seen that the carrier rate was very low and the prevalence of FMF was 0.15%, according to the common mutations of the MEFV gene in Adıyaman, Southeast Anatolia, Turkey.

Bcıı—RFLP profiles for serum amiloid A1 and mutated MEFV gene prevalence in chronic renal failure patients requiring long-term hemodialysis

Background and aim: There is an increased mortality risk in long-term hemodialysis patients of renal failure due to the chronic inflammation. The relationship between the chronic renal failure (CRF) and the role of familial genetic markers remains incompletely understood. In the current study, it was aimed to find out the prevalence of common MEFV gene mutations and BcII polymorphism in serum amyloid A1 (SAA1) gene in chronic renal patients (CRF) who require long-term hemodialysis. Method: Current cohort includes 242 CRF patients and 245 healthy individuals from the same population. Total genomic DNA was isolated from peripheral blood–EDTA samples and genotyping of target MEFV gene was carried out by reverse hybridization Strip Assay and real-time techniques. The SAA1 gene was genotyped by the BclI-RFLP method. Results: Increased mutated MEFV genotypes were found in current CRF patients when compared with the control group from the same ethnicity and the difference was statistically significant (Table 2) (OR: 4.9401, 95% CI: 3.0694–7.9509), p < 0.0001. The most frequent point mutations were M694V and E148Q. The mutated T allel frequency in the SAA1 gene was also different when compared with the healthy controls and the difference was found to be statistically significant (χ2: 13.18; p = 0.000). Conclusions: The current results indicate the germ-line mutations in both genetic biomarkers (MEFV and SAA1 genes) that are related to inflammation and amyloidosis processes may play a crucial role in CRF pathogenesis due to the long-term chronic inflammation.

MEFV gen mutasyonlarının tüberküloza direnç ile olası ilişkisi

Aim. Mycobacterium tuberculosis infection is a critical public health problem all over the world. T-helper 1 cells play an important role in the pathogenesis of tuberculosis. There is an increased activity of T-helper 1 in Familial Mediterranean Fever (FMF) patients and carriers. Based on immunity, we undertaken this study to evaluate a possible association of MEFV gene mutations with resistance to tuberculosis. Method. This study was performed with 51 patients (23 females, 28 males) applied to Cumhuriyet University Medical Faculty Chest Diseases Department between 2007 and 2009 and diagnosed with tuberculosis by physical examination, microbiological and radiologic analysis and 57 controls (26 females, 31 males). In these groups, 12 common MEFV gene mutations were researched using revers hybridisation FMF Strip Assay (ViennaLab Labordiagnostika, Vienna, Austria) technique. Results. A significant difference was not detected between patient and control groups in terms of distribution of MEFV mutations (p>0.05). There were 22 MEFV gene mutations (43.1%) in patient group. Homozygous mutation was not detected in this group. All mutations in patient group were heterozygous. There was also no homozygous mutation in control group and total 29 (50.8%) heterozygous mutations were detected. Conclusion. Our results suggested that the mutation frequency of MEFV gene in tuberculosis patients was not significantly different from healthy population. FMF mutations may effect the survive of tuberculosis but not sicken.

Idiopathic Uveitis and Familial Mediterranean Fever: Is There Any Relationship?

Introduction. Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by attacks of fever and polyserositis. FMF is often associated with other autoimmune diseases such as rheumatoid arthritis, polyarteritis nodosa (PAN), and Behcet. Uveitis is an inflammatory process caused by underlying infectious and inflammatory disorders. This study investigates the probable relationship between idiopathic uveitis and FMF. Methods. Patients with idiopathic uveitis were analyzed for the 12 most common MEFV mutations (P369S, F479L, M680I(G/C), M680I(G/A), I692del, M694V, M694I, K695R, V726A, A744S, R761H, E148Q) by a reverse hybridization assay (FMF StripAssay,Vienna lab,Vienna, Austria). Results. 12 patients with idiopathic uveitis were enrolled in this study. 10 of them were female. The youngest patient was a 7-year-old child and the oldest was 57. The most common complaints of patients were blurred vision and then eye redness. One patient was heterozygous for R761H. Genetic analysis of the 12 most common MEFV mutations in the patients with idiopathic uveitis didnot have any positive results. Conclusion. According to the analysis of the 12 most common MEFV gene mutations, FMF is not an underlying cause of idiopathic uveitis. On the other hand, uveitis merely could not be the first presentation of FMF.

The rate of MEFV gene mutations in hematolymphoid neoplasms

The aim of this study was to determine the rate of MEFV gene mutations, the gene responsible for familial Mediterranean fever (FMF), in patients with hematolymphoid neoplasm. The rate of the five most common MEFV gene mutations (M694V, M680I, V726A, M694I and E148Q) was determined in 46 patients with hematolymphoid neoplasm. We found a high frequency of carriers in patients with multiple myeloma (60%) and acute lymphocytic leukaemia (33.3%), whereas patients with chronic lymphocytic leukaemia (9%) and non-Hodgkin lymphoma (5%) had a low mutation carrier rate. There is no MEFV gene mutation in patients with Hodgkin lymphoma. Furthermore, the statistically significant predominance of strong heterozygous mutations such as M694V and M680I in patients with hematolymphoid neoplasm; none had own and/or family history compatible with FMF, is interesting. In conclusion, we found a high frequency of carriers for MEFV gene in patients with multiple myeloma and acute lymphocytic leukaemia. The data of our study may provide some new insights in understanding of individual genetic differences in susceptibility to these neoplasms.

Molecular analysis of MEFV gene in Iranian children with Familial Mediterranean fever

Objectives Familial Mediterranean fever is an autosomal recessive disorder characterized by recurrent attacks of fever and painful inflammatory manifestations in one or two sites. It is an ethnically restricted genetic disease, found commonly among Mediterranean population, as well as Armenians, Turks, Arabs and Jews. The disease is caused by mutations in the MEFV gene, encoding the Pyrin protein. The objective of this study was to identify the frequency of five common MEFV gene mutations in Iranian children with Familial Mediterranean fever. Methods Thirty unrelated children with clinical manifestation of Familial Mediterranean fever from various parts of Iran were selected and screened for the most common 5 MEFV mutations (M694V, M694I, M680I, V726A and E148Q). Results The most frequent mutation was M694V (53.3%), followed by M694I (23.3%) and E148Q (13.3%) mutations. We could not detect any mutations in 10% of our patients.

High frequency of MEFV gene mutations in patients with myeloid neoplasm

We aimed to investigate the rate of MEFV, the gene mutated in familial Mediterranean fever, mutations in patients with myeloid neoplasm and to determine if known mutations of MEFV cause a tendency for myeloid neoplasms. The frequency of the five most common MEFV gene mutations (M694V, M680I, V726A, E148Q and M694I) was determined in 26 patients with myeloid neoplasm. We identified 1 homozygous (E148Q/E148Q), 1 compound heterozygous (M694V/E148Q) and 5 heterozygous MEFV gene mutations; none had their own and/or family history compatible with familial Mediterranean fever. The mean overall mutation rate was 0.269. We found a high frequency of carriers in patients with myelodysplastic syndrome (66.6%), polycythemia vera (33.3%) and acute myeloid leukemia (28.6%). However, there was no MEFV gene mutation in patients with chronic myeloid leukemia. In conclusion, this study reports for the first time a possibly high prevalence of MEFV gene mutations in patients with myeloid neoplasm, especially myelodysplastic syndrome, polycythemia vera and acute myeloid leukemia. Our findings could open new perspectives for MEFV gene mutations in myeloid neoplasms and its association with tumor promotion. Further research is needed to determine the actual role of MEFV gene mutations in these malignancies.

Common MEFV gene mutations in children with FMF in Diyarbakır, Turkey

Common MEFV gene mutations in children with FMF in Diyarbakır, Turkey

Common MEFV gene mutations in children with FMF in Diyarbakır, Turkey

Familial Mediterranean Fever (FMF) is an autosomal recessive disease that clinically characterized by periodic abdominal pain, fever and arthralgia. Wide variety of mutations have been described in MEFV gene which is known to be responsible from FMF. In present study, 12 MEFV mutations [E148Q, P369S, F479L, M680I (G/C), M680I (G/A), I692del, M694V, M694I, K695R, V726A, A744S, R761H] have been screened. DNA samples were obtained from a total of 332 children, who were clinically suspected as FMF. Mutation analyses of MEFV gene were carried out with reverse hybridization method. In 113 children (mean age 11.5 years), mutations have been detected. In 60 children E148Q (4 homozygous), in 19 M694V (4 homozygous), in 16 P369S (none), and in 13 children V726A (none homozygous) mutations were detected. Among Familial Mediterranean Fever -suspected 332 children 104 fulfi lled diagnostic criteria for FMF and detected MEFV gene mutations with decreasing frequency were; E148Q (30.8%), M694V (18.3%), P369S (10.6%), V726A (8.6%), A744S (2.9%), R761H (2.9%), M694I (1.9%), K695R (1.9%) and I692del (1.0%), respectively. No mutation was detected in 15 (14.4%) FMF children while, two different MEFV mutations were detected together in 13 (12.5%) patients and these patients were accepted as a compound heterozygous. In conclusion, in our patients E148Q mutation was found higher than M694V mutation that has been detected commonly in patients with FMF. The difference may result from demographic features or used methods.

Clinical and molecular analysis of common MEFV gene mutations in familial Mediterranean fever in Sivas population

Familial Mediterranean fever (FMF) is the most frequent hereditary inflammatory disease characterized by self-limited recurrent attacks of fever and serositis. The aim of the current study is to determine the frequency of the mutations in 365 suspected FMF patients and to reveal whether there is a correlation between genotype and phenotype of these patients. All patients were clinically examined according to Tell-Hashomer FMF criteria and were screened genetically in terms of common 12 Mediterranean fever gene (MEFV) mutations. Various point mutations were detected in 270 (74%) patients. The most frequent mutation was M694V (26.85% of the alleles) and was followed by E148Q (15.55%), M680I (G/C) (9.62%) and V726A (7.96%). Patients who bear M694V homozygous mutation had most severe disease phenotype and high risk for amyloidosis (P = 0.04). Our results indicate that Sivas population has a wide range of heterozygous mutated carriers of MEFV gene and there is a high frequency of E148Q allele when compared to the other Mediterranean groups.

Analysis of Familial Mediterranean Fever Gene Mutations in 202 Patients with Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is an autosomal recessive disorder, caused by mutations in MEFV gene that encodes pyrin protein. In this study, we analyzed the most common five mutations in MEFV gene of 202 patients who were diagnosed formerly as FMF according to Tel-Hashomer criteria. The results of genetical analysis, clinical symptoms, and demographical aspects of those patients were evaluated retrospectively. Between the dates of February 2005 and March 2007, we analyzed five common MEFV gene mutations, which were M680I, M694V, M694I, V726A, and E148Q, in 202 patients by the PCR-ELISA method in our medical genetics laboratory. The most frequent mutation detected in our patients was M694V, and other mutations according to frequency were E148Q, M680I, V726A, and M694I. The detected mutations were homozygous in 45 of the patients (22.2%), heterozygous in 103 (51%), compound heterozygous in 52 (25.8%), and in 2 patients (1%) complex alleles were defined. The most common symptom was abdominal pain (80.4%) and other symptoms, respectively, were fever (57.8%), arthralgia (36.7%), chest pain (4.5%), and skin rash (2%). Amyloidosis was present in seven patients, and five of them had M694V mutation (homozygous), one of them had E148Q (heterozygous) mutation, and the other one had M694V/M694I mutation. In our patients, we defined 21 different genotypes of MEFV gene and the most common mutation was M694V. The most common symptoms were abdominal pain and fever. We detected significant correlation between the M694V, E148Q, and V726A mutations and clinical findings.

MEFV gene is a probable susceptibility gene for Behçet's disease

Objective: Behçet's disease (BD) is a rare, chronic, multisystem inflammatory disorder. The prevalence of BD is higher in the Middle Eastern and Mediterranean populations. Another chronic inflammatory disease, familial Mediterranean fever (FMF), is also known to be highly prevalent in these populations. The prevalence of BD is higher in the FMF patient population than in populations known to be rich in BD . Both BD and FMF have some pathophysiological features in common and they result from inappropriate activation of neutrophils. Clinical manifestations of both diseases can mimic each other and the coexistence of both diseases in the same patient has been reported. Given that BD and FMF have similar pathophysiological, epidemiological, and clinical features, we hypothesized that the gene responsible for FMF, MEFV, may also play a role in the pathogenesis of BD.Methods: Forty‐two BD patients who had no symptoms and family history for FMF and 66 healthy controls were screened for common MEFV gene mutations (E148Q, M680I, M694V, and V726A).Results: Fifteen patients (36%) displayed MEFV mutations (nine M694V, five E148Q, and one M680I) and mutation rates were significantly elevated compared to 66 (11%) healthy controls (p = 0.0034).Conclusion: The occurrence of frequent MEFV mutations in BD patients suggests that the MEFV gene is involved in the pathogenesis of Behçet's disease.