MEFV Gene Mutations Research Articles

Familial Mediterranean Gene (MEFV) Mutation in Parents of Children with Familial Mediterranean Fever: What Are the Exceptions?

Objectives Familial Mediterranean Fever (FMF) is one of the most prevalent periodic fever syndromes; MEFV, the responsible gene for the disease, is in the short arm of chromosome16. In the considerable count of the FMF patients, only one mutation is found in the MEFV and parents, who were the obligatory carriers for that mutation, were asymptomatic. The aim of this study was to evaluate these asymptomatic parents in regard to mutation in MEFV gene and similarity between parents and offspring patients. Methods In this cross-sectional study, asymptomatic parents of FMF patients enrolled the study were referred to periodic fever clinic or pediatric rheumatology clinic of Tehran University of Medical Sciences. The patients should have at least one mutation in MEFV gene and none of them had any family history of autoinflammatory disease. Twelve mutations in MEFV gene were assessed in the parents by Vienna Lab FMF Strip Assay kit by MAS PCR/Reverse hybridization. Results Forty-three patients and their parents participated in the study. Sixty-three percent (27) of patients were male. Onset of disease symptoms in 31 patients (72%) was before 4 years of old. Nine (21%) of the patients had homozygote, 16 (37%) compound heterozygote, and 17(40%) heterozygote for MEFV mutation; there was a case of complex alleles mutations (2%). M694V/M694V in 4 patients (9%) was the most homozygote genotype, and M694V/R761H in 4 (9%) and E148Q in 7 (16%) were the most compound heterozygote and heterozygote genotype, respectively. M694V, M680I, and E148Q were the most mutation in the parents. Overall, 41 patients had mutations similar to their parents' mutation, except 2 whose parents had no mutation, but a patient did. Conclusion It seems that occurrence of new mutations in offspring is not prevalent among FMF patients and there are other reasons for different clinical presentation in similar mutation carriers. On the other hand, in ethnicities with high prevalence of FMF, new mutation in descendant may occur, infrequently.

Familial Mediterranean fever (periodic disease): history or a real problem

The review is devoted to the most common monogenic autoinflammatory disease – familial Mediterranean fever (FML) caused by MEFV gene mutation that occurs mainly in the representatives of certain ethnic groups and manifests itself as recurrent 6–72-hour attacks of pyretic fever accompanied by the phenomena of aseptic peritonitis, pleurisy, arthritis, and inflammatory rash. The disease can lead to a life-threatening complication, such as amyloidosis. FML is noted to be comorbid with a number of other inflammatory diseases: systemic vasculitis, chronic joint inflammatory diseases, and inflammatory bowel diseases. Emphasis is laid on the therapy aspects set out in the 2016 EULAR guidelines. The mainstay of treatment for FML is colchicine that prevents recurrences of the disease, minimizes the risk of amyloidosis, and should be prescribed immediately, once diagnosed. The paper deals with the definition of colchicine resistance that is observed in 5–10% of patients. Biological agents, among which interleukin-1 are most preferred, are now used to treat this category of patients. The high efficacy of these agents in patients with FML has been confirmed in randomized controlled studies.

MEFV gene mutations and clinical course in pediatric patients with Henoch-Schönlein purpura.

To determine the frequency of the MEFV gene mutations in pediatric patients diagnosed with HSP and to assess the effect of the MEFV gene mutations on their prognosis. Material and Methods. Ccross-sectional study; pediatric patients between 2-11 years diagnosed with HSP were included. These cases were investigated for 6 MEFV gene mutations (M694V, M680I, A744S, R202Q, K695R, E148Q). Eighty cases were included in the study of which 55% were male (n= 44). The mean age was 6.44 ± 2.52 years. Disease recurrence occurred in 9 patients, invagination in 5 patients and convulsion in 1 patient during follow-up. Approximately half of the patients received steroids. The MEFV gene mutations was not detected in 44 (55%) of the patients. There was a heterozygous mutation in 19 (22%). E148Q was found in 8 patients, M694V in 5 patients, A744S in 4 patients, and the R202Q heterozygous mutation in 2 patients. The M608I homozygous mutation was detected in 1 patient and the M694V homozygous mutation in 1 patient. The compound heterozygous MEFV gene mutations was found in 15 patients. The presence of the MEFV gene mutations was not correlated with the frequency of renal and gastrointestinal involvement and prognosis, the development of complications and the use of steroids. The presence of the MEFV gene mutations does not correlate with the clinical course and complication in Turkish pediatric patients with HSP.

Macular and choroidal thickness of children with Familial Mediterranean Fever gene mutation

Introduction: The present study aimed to evaluate macular and choroidal thicknesses in children with MEFV gene mutations.Methods: Thirty-five children with MEFV gene mutations and 40 healthy controls were included in the study. MEFV gene profiles for the current cohort were genotyped by Pyrosequencing and direct Sanger sequencing techniques. The thicknesses of the macular and choroid of each subject’s right eye were measured using spectral-domain optic coherence tomography.Results: Mean arteriolar and venular diameters were 95.75±11.98 µm and 127.61±10.44 µm in children with the MEFV gene mutations and 110.19±11.10 µm and 138.54±10.04 µm in control group respectively. Children with the MEFV gene mutations were found to have a significantly less mean arteriolar diameter (p<0.001), mean venular diameter (p<0.001), less macular thickness (p=0.016), and less choroidal thickness (p=0.014) compared to healthy controls. Conclusion: Children with the MEFV gene mutations had narrowing of the retinal arterioles, retinal venules, and macular and choroidal thinning. Future studies should aim to investigate endothelial dysfunction in children with Familial Mediterranean Fever by non-invasive and effective methods.

La fièvre méditerranéenne familiale

Familial Mediterranean Fever (FMF) is the most frequent monogenic auto-inflammatory disease. FMF is an autosomal recessive disease, which affects populations from Mediterranean origin and is associated with MEFV gene mutations encoding for the protein pyrin. Pyrin activation enhances the secretion of interleukin 1 by myelo-monocytic cells. Main features of the disease are acute attacks of serositis mainly located on the abdomen, less frequently on chest and joints, accompanied by fever and biological inflammatory markers elevation. Usually attacks last 1 to 3days and spontaneously stop. A daily oral colchicine intake of 1 to 2mg/day is able to prevent attack's occurrence, frequency, intensity and duration among most patients. Colchicine is also able to prevent the development of inflammatory amyloidosis, the most severe complication of FMF. This state of the art article will focus on the diagnosis of FMF, the treatment and an update on the pathophysiology including the recent described dominant form of MEFV-associated new auto-inflammatory diseases.

A novel single variant in the MEFV gene causing Mediterranean fever and Beh\xe7et\u2019s disease: a\xa0case report

BackgroundFamilial Mediterranean fever is an autoinflammatory disease of unknown etiology, characterized clinically by recurrent attacks of sudden-onset fever with arthralgia and/or thoracoabdominal pain and pathogenetically by autosomal recessive inheritance due to a mutation in the MEFV gene. Behçet’s disease is an inflammatory disease characterized by recurrent oral and genital aphthous ulcerations, uveitis, and skin lesions. Preliminarily, our literature review suggested that patients with familial Mediterranean fever who also have Behçet’s disease have only a single mutated familial Mediterranean fever gene. The MEFV gene mutation responsible for familial Mediterranean fever is probably a susceptibility factor for Behçet’s disease, particularly for patients with vascular involvement, and both disorders can occur concurrently in a patient, as in the present case.Case presentationA 10-year-old girl of Moroccan origin presented to our institution for genetic consultation for genetic testing of the MEFV gene. She had fever associated with abdominal and diffuse joint pain in addition to headache. These symptoms have oriented pediatricians to familial Mediterranean fever. The evolution was marked by Behçet’s syndrome symptoms. Sanger sequencing followed by complete exome sequencing analysis of the MEFV gene for the proband mutation revealed a novel variant. We conclude that the novel single variant c.2078 T > A (p.Met693Lys) could be responsible for the association of familial Mediterranean fever and Behçet’s disease.ConclusionTo the best of our knowledge, this is the first report of a new variant in exon 10 of the MEFV gene in a Moroccan family. This novel variant should be listed in the MEFV sequence variant databases.

Ankylosing Spondylitis Among Familial Mediterranean Fever Patients.

Familial Mediterranean Fever (FMF) is one of the most common hereditary auto-inflammatory diseases especially among Arabs, Armenians, Jews, and Turks characterized by recurrent attacks of fever, abdominal pain and arthritis.Whether the prevalence of ankylosing spondylitis (AS) is increased in FMF patients is a matter of debate. This review will summarize all the literature data relevant to this topic. We searched all the articles through PubMed and Embase databases from 1963 until 2017 addressing the relationship between AS and FMF patients. The prevalence of AS among FMF patients is highly variable. However, a significant relationship was found to exist between MEFV gene mutations and AS. Most patients with coexistent MEFV gene mutations and AS were human leucocyte antigen B27 (HLA-B27) negative. The effect of these mutations on AS severity and prognosis was not significant. Large based population studies are needed to further assess the existence of MEFV gene mutations among AS patients and their effect on the clinical course of the disease in addition to assessment of AS prevalence in patients with FMF.

Screening of the most common MEFV mutations in a large cohort of Egyptian patients with Familial Mediterranean fever

Background and aimFamilial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease (AID) characterized by self-limited inflammatory attacks of fever and serosal tissues inflammation. FMF is caused by mutations in the MEFV gene coding for pyrin, which is a component of inflammasome functioning in inflammatory response. The objectives of the investigation were to evaluate the clinical symptoms and screen the most common MEFV variants in the Egyptian FMF patients. Methods818 FMF patients were enrolled in this study based on clinical criteria. Three different screening molecular methods were used; ARMs, strip assay and direct Sanger sequencing. ResultsThe most frequent clinical presentations of the patients were abdominal pain, fever and arthritis. Most of the patients responded to colchicine therapy. MEFV gene mutations were detected in 60% of the patients. The most common mutations were; M694I (27.59%), M762A (16.84%), M680I (16.02%), E148Q (10.34%) and M694V (9.33%). ConclusionThis is the largest study on FMF from Egypt. Exon 10 of the MEFV gene recorded hot spot variants in the studied Egyptian FMF patients. We suggest screening for exon 10 as the first step in molecular characterization of FMF patients. Although none of the mutations in exon 10 and 2 were detected in 49.3% of our patients, despite all of them suffered from FMF symptoms and responded well to colchicines. This study recommends full sequencing to MEFV gene in these patients which may help to discover new mutations in Egyptian FMF patients and to design a local diagnostic kit.

Assesment of Common Exon 10 MEFV Gene Mutations in Patients with Refractory Rheumatoid Arthritis

Assesment of Common Exon 10 MEFV Gene Mutations in Patients with Refractory Rheumatoid Arthritis

Is there any relationship between human foamy virus infections and familial Mediterranean fever?

Background:Familial Mediterranean fever (FMF) is generally defined as an autosomal recessive disease, characterized by the automatic activation of the innate immune system in the absence of a detectable pathogenic stimulant. We hypothesize that the pathogenic factors, besides the genetic causes, may affect the development of FMF symptoms. To test this hypothesis, we examined the effects of human foamy virus (HFV) positivity on the occurrence of the clinical symptoms of FMF.Materials and Methods:Two hundred and twenty-two FMF patients with definitive diagnosis according to Tel Hashomer criteria (study group 1 [SG1]), 205 symptomatic FMF patients who had definitive diagnosis according to the same criteria but did not carry any of the 12 most commonly occurring MEFV gene mutations (study group 2 [SG2]), and 200 healthy individuals were included as control group (study group 3 [SG3]) in the study. The genetic analysis was applied in the Molecular Genetics Laboratory of the Department of Medical Biology, Faculty of Medicine, Ondokuz Mayıs University. This study was designed as a case-control study. HFV positivity was tested by amplifying the HFV bel1 gene sequence with polymerase chain reaction technique. Statistical analyses were conducted using SPSS version 23.0 software.Results:HFV positivity showed significant differences between the study groups (P = 0.002). While 43 (19.02%) of the 222 SG1 patients were positive for the HFV bel1 gene sequence, 33 (16.09%) of the 205 SG2 patients were positive for the same sequence. Only 15 (7.5%) of the SG3 participants were positive for the presence of HFV bel1 gene sequence.Conclusion:The results of our study suggested that HFV positivity can be a stimulant pathogenic factor of natural immune system which can cause the emergence of FMF symptoms.

First Report of Predominant MEFV Mutations in a Persian Children Population with Familial Mediterranean Fever: R202Q, M694V/I

This study evaluated the MEFV gene profile of in 50 children with familial Mediterranean fever (FMF) referred to Ali Asghar and Mofid Children Hospitals (Tehran, Iran) from 2012 to 2014; and it was the first to recruit full-length Sanger sequencing method for a considerable number of referral patients from all regions of Iran. The mean age of the patients was 7.5 years (range 3-23), and 56% of them were male. The children with FMF in this study were from different ethnic background including Azari (47%), Fars (34%), and others (19%); whose parents’ consanguinity was detected in 79% of cases. The body temperature at the time of the disease attack ranged from 38°C to 40°C with a two-week to six-month interval between the attacks, and a 1-10-day duration for each attack. The most prevalent clinical manifestations were fever (100%), abdominal pain (78%), chest pain (26%), joint pain (18.4%), and erythematous rash (2.6%), respectively. None of the cases had amyloidosis at the presentation time; 3 years followup of half of the cases, showed 100% response to colchicine with complete symptom relief and no proteinuria or renal failure. Approximately 32% experienced drug-induced side effects, the most common of which were gastrointestinal symptoms (especially diarrhea) and myopathy, respectively. From total of 50 patients assessed for the MEFV gene mutations, 29 (58%) were homozygous, 8 (16%) were compound heterozygous, and 13 (26%) were heterozygous. Overall, the most common allele variations were R202Q (24%), followed by E148Q (13%), M694V (11%), and M694I (11%), respectively. In conclusion, the dominance of R202Q, E148Q, M694V, and M694I mutations in our cases might be a useful guide for genetic-based approach to FMF in Persian pediatric population.

Increased Frequency of MEFV Genes in Patients with Epigastric Pain Syndrome.

Atypical clinical forms of familial Mediterranean fever (FMF) can be misdiagnosed as therapy-resistant epigastric pain syndrome (EPS) for they share many of the same clinical features, such as abdominal pain. Thus, we aimed to determined the frequency of FMF in patients who were followed with a diagnosis of therapy-resistant EPS. Seventy-five patients with therapy-resistant EPS and 20 controls were involved in the study. To detect the FMF in patients with therapy-resistant EPS, Tel-Hashomer criteria, family history of FMF were researched and recorded. We performed performed MEFV gene analysis on all patients. Forty-three patients with EPS (57.3%) had MEFV gene mutations and the carrier rate was 30.0%. The most common MEFV gene alteration was R202Q (55.8%), followed by E148Q (16.2%), R761H (16.2%), V726A (9.3%), M680I (9.3%) and M694V (4.6%). Rarely seen mutations in the Turkish population were also identified: K695R (2.3%), L110P (2.3%) and G304R (2.3%). Eight patients with EPS were diagnosed with FMF and started on colchicine therapy. Three patients with compound heterozygosities for three mutations, two patients with compound heterozygosities for two mutations (K695R/ V726A and R202Q/ R761H), one patient with homozygous R202Q, one patient with heterozygous R202Q mutation and one patient with non- R202Q heterozygous mutation (G304R/–) had clinical FMF symptoms and were started on colchicine therapy. Patients who have therapy-resistant EPS should also be questioned about FMF, especially in high risk populations.

Does thiol-disulphide balance show oxidative stress in different MEFV mutations?

Many studies have shown that oxidative stress levels increase in patients with Familial Mediterranean Fever (FMF). Thiols are a class of compounds that include a sulfhydryl group (-SH) and can react with free oxygen radicals to protect tissues. We aimed to investigate thiol-disulphide homeostatic status in FMF patients and examined the effect of different mutations in the MEFV gene on the thiol-disulphide balance. We investigated thiol-disulphide parameters in patients with FMF and healthy controls. To determine the differential effect of MEFV gene mutations on thiol-disulphide balance, subjects were divided into five groups based on homozygous or compound heterozygous exon 10 and nonexon 10 mutations. Tests of thiol-disulphide homeostasis were conducted using the automated spectrophotometric method. Patients with FMF had significantly lower native thiol [433.8 µmol/l (243.3-536.4) vs. 484.1µmol/L (340.2-612.3), p <0.001], total thiol levels [459.7µmol/L (281.3-575.4) vs. 529.9µmol/L (363-669.5), p<0.001], and disulphide levels [14.0µmol/l (2.7-33.3) vs. 24.4µmol/l (7.2-36.6), p<0.001] compared to the control group. Moreover, disulphide/native thiol (3.4 ± 1.7 vs. 4.7 ± 1.3, p < 0.001) and disulphide/total thiol (3.1 ± 1.4 vs. 4.3 ± 1.0 p < 0.001) were also detected lower in the FMF group compared to the control group. But the native thiol/total thiol ratios (93.6 ± 2.9 vs. 91.3 ± 2.1, p < 0.001) were higher in the FMF group. There was no significant difference between the native thiol, total thiol, and disulphide levels of individuals with nonexon 10 homozygous or compound heterozygous (Group 1), nonexon 10-exon 10 compound heterozygous (Group 2), exon 10 homozygous or compound heterozygous (Group 3), and heterozygous (Group 4) mutations. However, these parameters significantly differed from those of the healthy control group. Since no differences were found in our study between thiol and disulfide levels of Groups 1, 2 and 3, we believe that this rate cannot be shown as an indicator of oxidative damage in different mutations of FMFs. To the best of our knowledge, this study is the first study that demonstrates the effect of different FMF mutations on the thiol-disulphide balance.

Cardiac disease in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autoinflammatory disease manifested by inflammatory attacks of peritonitis, pleuritis, pericarditis accompanied by fever and arthritis. Mutations of MEFV gene results in pyrin dysfunction, which causes uncontrolled interleukin-1 beta production and triggers the inflammatory attacks. Inflammation persists even during attack-free periods in one-third of the FMF patients. Findings of elevated proinflammatory cytokine patterns during remission as well as inflammatory attacks indicate the continuous subclinical disease activity and inflammation. Chronic inflammation was thought to be related to the cardiovascular risk in FMF patients. Main cardiac manifestations reported in FMF are pericarditis, idiopathic recurrent pericarditis, pericardiac tamponade, coronary heart disease and abnormal cardiovascular reactivity. Cardiac involvement in FMF may often be related to secondary AA amyloidosis. Deposition of amyloid may lead to cardiovascular morbidity and mortality in FMF patients. Associations of several vasculitic disorders such as Immunoglobulin A-associated vasculitis, polyarteritis nodosa and Behcet's disease are common in FMF. Appropriate prophylactic treatment with colchicine is recommended to prevent from cardiovascular risks. For those resistant to colchicine, IL-1 inhibitor agents can be used. Associated vasculitis should be treated with immunosuppressive agents. This review article aims to compile information about cardiac disease in FMF and refer to recent studies on the topic.

The spectrum of Familial Mediterranean Fever gene (MEFV) mutations and genotypes in Iran, and report of a novel missense variant (R204H)

BackgroundFamilial Mediterranean Fever (FMF) is an autosomal recessive disorder, characterized by recurrent and self-limited episodes of fever, abdominal pain, synovitis and pleuritis. FMF as the most common inherited monogenic autoinflammatory disease mainly affects ethnic groups of the Mediterranean basin, Arab, Jewish, Turkish, Armenian North Africans and Arabic descent. Materials and methodsIn the present study, we selected 390 unrelated FMF patients according to the Tel-Hashomer criteria, and analyzed all patients for 12 most common mutations of MEFV gene by reverse hybridization assay (FMF strip assay). We also investigated exon 2 and 10 of MEFV gene in 78 patients by Sanger sequencing. ResultsAccording to strip assay results, at least one mutation was found in 234 patients (60%), and no mutation was found in other 156 patients (40%). The five most common mutations and allelic frequencies were M694V (13.6%), E148Q (10.4%), M694I (6.5%), V726A (4.1%), and M680I (3.8%). Moreover, we detected a novel missense variant (R204H, c.611 G > A) (SCV000297822) and following rare mutations among sequenced samples; R202Q, P115T, G304R, and E230K. ConclusionThis study describes the MEFV mutations spectrum and distribution in Iranian population, and shows different mutation patterns among Iranian ethnicities. Moreover, M694V is the most common MEFV mutation in Iran.

Comparing D-dimer status in children with familial Mediterranean fever during and in between acute attacks

Aim of the workTo compare the D-dimer status in children with familial Mediterranean fever (FMF) during, and in between acute attacks. Patients and methodsThe study included 50 children with FMF classified into group I (15 patients during acute attack) and group II (35 patients during attack free period) as well as and 20 matched controls. D-dimer was determined in all study population. Pattern and type of FMF gene mutation were reported from patients’ files. ResultsThe mean age of the patients was 8.7±2.8years, disease duration 4.4±2.5years and they were 28 males:22 females (1.3:1). In group I, the erythrocyte sedimentation rate (48.5±28.6mm/1st h) and aspartate transaminase (28.5±5U/L) were significantly increased compared to group II (26.6±14.7mm/1st h and 25.7±2.7U/L; p=0.012 and p=0.014 respectively). Positive D-dimer was significantly reported in 72% of FMF patients compared with 35% of control (p=0.006). There was significant difference between frequency of positive D-dimer in group I (86.7%) and group II (65.7%) compared to (35%) in control (p=0.005 and p=0.048, respectively), without a significant difference in D-dimer frequency between group I and group II patients (p=0.18). Fever and abdominal pain were significantly more frequent in patients with positive (100% and 97.2%) compared to negative D-dimer (78.6% and 71.4%) (p=0.02). No significant association was found between positive D-dimer and specific types of MEFV gene mutation. ConclusionD-dimer was significantly positive in FMF patients compared to control. These results raise the possibility of thrombosis in FMF patients regardless the presence or absence of acute attack.

MEFV Mutation Frequency in Pediatric Patients with Familial Mediterranean Fever and its Relationship with Clinical Phenotypes in Marmara Region of Turkey

Background: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterised by recurrent fever, peritonitis, pleuritis, and arthritis. Three hundred and seventeen mutations and polymorphisms related to FMF have been identified to date. Objectives: The evaluation of the distribution of genetic mutations in children whose FMF study was conducted in Marmara region in Turkey and the relationship between clinical findings and the mutation was aimed in the study. Methods: The files of all patients whose pre-diagnosis of FMF and MEFV gene mutation analysis were made, were evaluated retrospectively. The results of the MEFV gene mutation analysis of the patients were screened retrospectively. Common MEFV gene mutation analyses were studied. The age, gender, presenting complaints, and histories of the patients were obtained from the files and records. Results: A total of 150 patients were included in the study. The mean age of the cases was 9.37 ± 4.43 years; 78 were female and 72 were male. Sixty-seven (44.7%) of the cases had abdominal pain, 30 (20%) had arthralgia, 25 (16.7%) had fever, 2 (1.3%) had chest pain, and 30 (20%) had other complaints. While the mutation with the highest frequency was R202Q (37.2%), it was observed that allele frequencies following this were E148Q (23.4%), M694V (21.9%), V726A (5.1%), and M680I (2.9%). Abdominal pain was detected as the most frequent presenting complaint. Conclusions: Although M694V gene mutation is the most frequently observed mutation in Turkey, we identified that the most frequent gene mutations were R202Q and E148Q in this study. This situation may be because most of our patients were from Anatolian regions where there are many ethnic groups. When the distribution of genotypes was examined by complaint, the most frequent complaint identified in all gene mutations was abdominal pain.

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.

Small Intestinal Bacterial Overgrowth Affects the Responsiveness to Colchicine in Familial Mediterranean Fever.

Objective Familial Mediterranean fever (FMF) is an autosomal recessive disease due to a MEFV gene mutation. Since Helicobacter pylori infection has been described to increase the severity and frequency of FMF attacks, we evaluate if overgrowth of small intestinal bacterial (SIBO), associated with a release of bacterial products, can affect the response to colchicine in FMF patients poorly responsive to colchicine. Methods We revised our Periodic Fever Centre database to detect FMF patients who were poorly responsive to colchicine, without a well-defined cause of drug resistance. They were evaluated for SIBO presence, then treated with decontamination therapy. Results Among 223 FMF patients, 49 subjects show colchicine resistance, and no other known causes of colchicine unresponsiveness has been found in 25 patients. All 25 patients underwent glucose breath test; 20 (80%) of them were positive, thus affected by SIBO. After a successful decontamination treatment, 11 patients (55%) did not show FMF attacks during the following three months (p < 0.01), while 9 of them revealed a significant reduction of the number of attacks compared to three months before (p < 0.01). Conclusion The SIBO eradication improves laboratory and clinical features of FMF patients. Thus, patients with unresponsiveness to colchicine treatment should be investigated for SIBO.

MEFV gene mutation frequency and distribution of mutations in FMF patients: Analysis of a large group of patients from a single center

MEFV gene mutation frequency and distribution of mutations in FMF patients: Analysis of a large group of patients from a single center