Mediterranean Fever Gene Mutations Research Articles

Factors triggering familial mediterranean fever attacks, do they really exist?

Several possible factors are hypothesized to trigger familial Mediterranean fever (FMF) attacks; however, there is no consensus on this matter. We aimed to identify these triggering factors and analyze their relationship with the Mediterranean fever gene mutation status. We prepared a questionnaire that included the most commonly mentioned possible trigger factors of familial Mediterranean fever. We administered a questionnaire to 882 patients. We used a questionnaire assessing the following: psychological stress, consumption of tea and coffee, relationship with menses, menopause and post-menopausal alleviation, seasonal changes, traveling for long durations, relocation, starvation, sleeplessness, cold exposure, fatigue, wind exposure, and humidity. The most frequent triggering factor for familial Mediterranean fever attacks was psychological stress (75.2%). Cold exposure was a statistically significant trigger in patients with exon 10 mutations. Humidity was a statistically significant trigger in patients with exon 2 mutations. Seasonal changes, traveling for long durations, relocation, and cold exposure were statistically significant triggers of familial Mediterranean fever attacks in patients with homozygous M694V mutations. Identifying trigger factors can lead to better preventive measures and personalized therapies to decrease familial Mediterranean fever attacks. Patients can significantly decrease the number of familial Mediterranean fever attacks they experience by managing psychological stress and avoiding physical factors such as cold exposure and fatigue. Determining the relationship between trigger factors and patients' Mediterranean fever gene mutation status can lead to personalized therapy for the prevention of familial Mediterranean fever attacks.

Course of COVID-19 in patients carrying different MEFV mutations of familial Mediterranean fever

Familial Mediterranean Fever (FMF) is a genetic auto-inflammatory disease. Mutations in the Mediterranean fever (MEFV) gene cause inappropriate immune system triggering, leading to inflammatory episodes in the peritoneum, pleura, and joints. In the severe Coronavirus disease-19 (COVID-19) picture, the hyperimmune response and inflammatory process develop with exacerbation of the clinical condition. FMF disease, the drugs used in its treatment, and the possible effects of different genetic MEFV mutations on the course of COVID-19 arouse interest. In this study, 158 FMF patients with different MEFV gene mutations were evaluated using an online survey method in terms of COVID-19 course, hospitalization, additional comorbidities, and COVID-19 vaccination status. Participants were asked 21 questions and the data provided were compared between FMF MEFV gene mutations. 104 out of 158 cases did not get COVID-19. 9 of 54 cases who got COVID-19 were hospitalized. No statistically significant difference was found between MEFV gene mutations when evaluated and compared in terms of susceptibility to COVID-19, vaccination status, and presence of additional chronic diseases and comorbidities. The present study provides guidance on the role of FMF genetic mutations in the course of COVID-19. Our study may suggest that FMF MEFV gene mutations do not have a protective role against COVID-19. The results also may suggest that, as an inverse effect, MEFV gene mutations do not increase the risk of hyper-immune response and severe acute respiratory syndrome (SARS), which play a role in the severe course of COVID-19.

Familial Mediterranean fever and microRNAs.

Familial Mediterranean fever (FMF) is an inherited disorder caused by the gain of function mutations in MEFV (MEditerranean FeVer) gene loci. FMF affects more than 100,000 people worldwide and generally seen in the eastern Mediterranean region and causes the lifelong diseases which have a significant effect on the patient's life quality and health systems. The identification of low penetrant or heterozygous MEFV gene mutations in clinically diagnosed FMF patients was considered that epigenetic or environmental factors may display a role in FMF pathogenesis. Epigenetics might be defined as heritable changes that affect gene expression without any changes in the genome. MicroRNAs (miRNAs) are the main group of small noncoding RNAs, and an important element of epigenetic mechanisms and their discoveries revolutionized our knowledge about biological processes, such as malignant, infectious and autoimmune mechanisms, and contributed to the development of the epigenetic areas. In this review, the studies focusing on the roles of miRNAs in FMF pathogenesis in the last decades were examined and the importance of miRNAs as therapeutic agents which are promising for diagnosis and treatment was discussed.

Frequency of Familial Mediterranean Fever Gene Mutation in Patients Presenting With Joint Pain and Diagnosed With Acute Rheumatic Fever.

Introduction Acute rheumatic fever (ARF) is a non-suppurative systemic inflammatory disease that manifests 1-5 weeks following a Group A beta-hemolytic streptococcal infection. On the other hand, familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized as an autosomal recessive disease, with affected individuals having pathogenic mutations in the Mediterranean fever gene(MEFV)gene located on the short arm of chromosome 16. FMF and ARF have overlapping symptoms and signs, and both disorders are common in Turkey. In ARF, the target organ is the heart, while in FMF, the target organ is the kidney; both organs can benefit from prophylactic measures. Our study aims to determine the frequency of the FMF gene mutation in patients with ARF in Turkey and detect any overlapping conditions. Method Patients who were diagnosed with a first-attack ARF between May 2015 and May 2018 were retrospectively screened. Patients who underwent MEFV gene analysis considering FMF in the differential diagnosis were included in the study. Results In this study, no statistical difference was found between the presence of MEFV gene mutations, carditis, high anti-streptolysin-O antibody (ASO) levels, and the groups with monoarthritis, polyarthritis, and polyarthralgia (p >0.05). Conclusions In conclusion, patients with ARF should be evaluated for FMF to avoid irreversible complications.

Possible Association of Mutations in the MEFV Gene with the Intestinal Phenotype of Behçet's Disease and Refractoriness to Treatment.

Mediterranean fever (MEFV) gene mutations are responsible for familial Mediterranean fever (FMF) and associated with other inflammatory diseases. However, the effects of MEFV gene mutations on intestinal Behçet's disease (BD) are unknown. In this study, we investigated these mutations and clinical features in patients with intestinal BD. MEFV gene analysis was performed in 16 patients with intestinal BD, 10 with BD without intestinal lesions, and 50 healthy controls. Clinical features of patients with intestinal BD were retrospectively assessed. The rates of MEFV gene mutations in patients with intestinal BD, BD without intestinal lesions, and healthy controls were 75%, 50%, and 38%, respectively. Only 2 of 12 patients with intestinal BD harboring MEFV gene mutations (17%) were controlled without immunosuppressive treatment, while 8 patients (67%) required therapy with tumor necrosis factor (TNF) inhibitors. Among patients with intestinal BD without MEFV gene mutations (four patients), three (75%) were controlled by the administration of 5-aminosalicylic acid with or without colchicine, and one (25%) required TNF inhibitors. All patients who underwent intestinal resection had MEFV gene mutations. Immunohistochemical analysis and in situ hybridization with interleukin-1β (IL-1β) showed a high expression of IL-1β only in injured areas, suggesting that IL-1β may be involved in the formation of ulcers in patients with intestinal BD carrying MEFV gene mutations. Mutations in the MEFV gene may be associated with intestinal lesions of BD and refractoriness to treatment.

Periodic Fever in Children: A Report of Three Unusual Cases

Introduction: Periodic fever syndrome (PFS) is a rare monogenic autoinflammatory disease group. The innate immune system abnormalities have a characteristic onset and spontaneous inflammation without any infectious or autoimmune trigger. It differs from autoimmune disorders (e.g., systemic lupus erythematosus (SLE)) occurring due to a defect in the adaptive immune system with auto-antibodies. Case Presentation: The clinical features of three patients presented with a periodic pattern of fever and a different constellation of symptoms were investigated. The final diagnosis of Periodic fever syndrome was reached based on standard diagnostic criteria and genetic testing. All three cases were observed to present with recurrent fever episodes at an interval of 6 - 12 weeks, 3 - 4 weeks, and one month, respectively. The first patient, presenting with a diffuse erythematous plaque-like lesion along the calf with severe calf pain and tenderness with signs of meningeal irritation, was diagnosed with a tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS) like phenotype. The genetic panel was negative in this case. The second patient presenting with recurrent pharyngitis, cervical adenitis, and tonsillitis unresponsive to antibiotics was diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. The last patient presenting with recurrent monoarthritis, hepatosplenomegaly, and a positive Mediterranean fever (MEFV) gene mutation was diagnosed with familial Mediterranean fever (FMF). All three patients had normal growth and development. Conclusions: Although periodic fever syndrome was an uncommon entity, it was recommended that this syndrome should be considered when a patient presented with recurring fever episodes with a characteristic constellation of symptoms.

Immunogenic Potential of the Mediterranean Fever Gene in Patients with Coronavirus Disease: A Cross-Sectional Study.

In December 2019, an outbreak of pneumonia caused by the novel coronavirus disease 2019 (COVID-19) became a pandemic and caused a global health crisis. This study evaluates the immunogenic potential of the Mediterranean fever (MEFV) gene in patients with COVID-19. A cross-sectional study was conducted from March to April 2020 in various COVID-19 referral centers in Ardabil, Iran. Blood samples of 50 hospitalized patients with confirmed COVID-19 were evaluated for MEFV gene mutation using the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) and Sanger sequencing. Statistical analysis was performed using SPSS software, version 22.0. Mutations of the MEFV gene were found in 6 (12%) of the patients. All mutations were heterozygous, and no homozygous or compound heterozygous forms were detected. The total mutant allele frequency was 6% and the carrier rate was 12%. The most common allele of the MEFV variant was E148Q, detected in 3 (6%) patients. No mutant variant of the MEFV gene was detected in deceased patients. None of the mutation carriers had familial Mediterranean fever (FMF) symptoms or a family history of FMF. MEFV gene mutations may have immunogenic potential in patients with COVID-19. A preprint version of this article has already been published at https://www.researchsquare.com/article/rs-69373/latest.pdf.

The Mediterranean Fever Gene Mutations and Its Association with HRQoL, Depression and Fatigue in Patients with Familial Mediterranean Fever Associated Spondyloarthropathies

The Mediterranean Fever Gene Mutations and Its Association with HRQoL, Depression and Fatigue in Patients with Familial Mediterranean Fever Associated Spondyloarthropathies

Does having MEFV gene sequence variants affect the clinical course and colchicine response in children with PFAPA syndrome?

Colchicine seems to be an effective and safe treatment modality in PFAPA treatment. It led to a change in the nature of the attacks either in the frequency, duration, or severity of the attacks in 95.1% of the patients. This study has shown that having MEFV gene sequence variants did not affect the clinical course or response to colchicine. We recommend that colchicine should be considered in all PFAPA patients to see the response of the patient, irrespective of the MEFV gene mutations. • Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common periodic fever syndrome in the world. Familial Mediterranean fever (FMF) is the most common cause of periodic fever syndrome in Turkey. • Colchicine has become a new treatment option in PFAPA. •Some PFAPA patients have Mediterranean fever (MEFV) gene variants, and it is speculated that PFAPA patients with MEFV gene mutations respond better to colchicine. •The aim of this study was to look for this hypothesis. We have seen that the clinical phenotype and colchicine response of PFAPA patients were not affected by MEFV gene sequence variants.

Investigation of the effect of vascular endothelial growth factor gene 936 C/T polymorphism in familial Mediterranean fever patients

Objectives: This study aims to investigate the effect of vascular endothelial growth factor (VEGF) gene 936C/T polymorphism (rs3025039) on the appearance of phenotypic characteristics of familial Mediterranean fever (FMF) patients that differ with respect to MEditerranean FeVer (MEFV) gene mutations. Here, we investigated a single functional polymorphism in the VEGF gene. Methods: The study group consisted of 223 FMF patients with definite diagnosis according to Tel-Hashomer criteria who carried MEFV gene mutations, while 208 FMF patients with definite diagnosis of FMF but without any mutations, making up the control group, were included in the study. The VEGF gene 936C/T polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: Genotype and allele frequencies of the VEGF rs3025039 polymorphism between the two groups were significantly different (p = 0.03 and p = 0.011, respectively). The TT genotype was found to be more frequent in the study group than in controls (4.9% vs. 3.3%, respectively). Conclusions: Our results seem to indicate that the VEGF 936C/T polymorphism affects the appearance of the phenotypic characteristics of FMF. It is possible that other variants of this gene may also have similar effects.

Can RDW be used as a screening test for subclinical inflammation in children with FMF? Is RDW related to MEFV gene mutations?

Subclinical inflammation, an insidious feature of familial Mediterranean fever (FMF), can lead to life-threatening amyloidosis. We aimed to investigate acute phase reactants and complete blood count parameters to identify a useful marker for subclinical inflammation in children with FMF. A secondary aim was to identify an association between subclinical inflammation and specific Mediterranean fever (MEFV) gene mutations. This study included 420 pediatric patients with FMF. Laboratory parameters of patients during the attack-free period and MEFV gene mutation analyses were recorded. Of the 420 patients, 88 (21%) had subclinical inflammation. Of those with subclinical inflammation, 48 (55%) had mutations in exon 10, 36 (41%) had M694V mutation, and 10 (11%) had M694V homozygous mutation. Red cell distribution width (RDW) value was higher in exon 10, M694V, and M694V homozygous mutations compared to other mutations. RDW was positively correlated with serum amyloid A (SAA) (r = 0.390, p = 0.0001). Analysis of a receiver-operating characteristic curve of RDW revealed that its optimal cut-off value for subclinical inflammation was 12.69%, its sensitivity was 64.10%, and its specificity was 50.90%. The area under the curve was 0.616 (p = 0.004, 95% confidence interval = 0.538-0.695). We suggest that RDW can be used as a screening test as a marker of subclinical inflammation. A high RDW value should alert the clinician about subclinical inflammation in FMF children's patients with M694V (heterozygous, homozygous, compound heterozygous) mutation. Key Points • Subclinical inflammation in FMF patients can lead to amyloidosis. • RDW can be a predictor of subclinical inflammation. • RDW can be used as a screening test for subclinical inflammation in FMF patients with M694V mutation.

Acute Recurrent Pericarditis as the Inaugural Manifestation of Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is an inherited autosomal recessive disorder commonly found among individuals of Mediterranean or Middle Eastern descent and caused by Mediterranean Fever gene (MEFV) mutations on chromosome 16. It is the most frequent periodic febrile syndrome among the autoinflammatory syndromes. Typical febrile attacks include serosal inflammation, but although FMF is characterized by recurrent polyserositis, there is a little documentation of pericardial disease among patients.We report the case of a patient who presented recurrent pericarditis. Each episode occurred with a high fever and elevation of the C-reactive protein level. Treatment with colchicine was effective. The patient was found to be heterozygous for the V726A mutation.LEARNING POINTSThe aetiology of recurrent pericarditis is still largely unknown.The occurrence of pericarditis as a manifestation of familial Mediterranean fever is controversial.

Real-Life Data From the Largest Pediatric Familial Mediterranean Fever Cohort.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting phenotypic heterogeneity. It is a clinically diagnosed disease supported by MEditerranean FeVer (MEFV) gene mutation analysis. However, the phenotype-genotype correlation is not yet established clearly. We aimed to determine the clinical findings, phenotype-genotype correlation, and treatment outcomes within a large pediatric FMF cohort. The medical charts of children with FMF who were diagnosed and followed up at the eight pediatric rheumatology units were reviewed retrospectively. All patients in the cohort were analyzed for sequence variants in exon 2,3,5 and 10 of the MEFV gene. Patients without any mutations or with polymorphisms including R202Q were excluded. A total of 3,454 children were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 12.1 ± 5.2, 5.1 ± 3.8, and 7.3 ± 4.0 years, respectively. Of 3,454 patients, 88.2% had abdominal pain, 86.7% had fever, 27.7% had arthritis, 20.2% had chest pain, 23% had myalgia, and 13.1% had erysipelas-like erythema. The most common MEFV mutation patterns were homozygous (32.5%) and heterozygous (29.9%) mutations of exon 10. Homozygous M694V was present in 969 patients (28.1%). Allele frequencies of common mutations were M694V (55.3%), M680I (11.3%), V726A (7.6%), and E148Q (7.2%). Children carrying homozygous or compound heterozygous exon 10 mutations had an earlier age of disease onset (4.6 vs. 5.6 years, p = 0.000) and a higher number of attacks per year (11.1 vs. 9.6, p = 0.001). Although 8% of the patients had a family history of amyloidosis, 0.3% (n = 11) had the presence of amyloidosis. M694V homozygosity was detected in nine patients who developed amyloidosis. Colchicine resistance was present in 4.2% of our patients. In this largest pediatric cohort reviewed and presented to date, patients with exon 10 mutations, particularly the M694V homozygous mutation, have been demonstrated earlier disease onset, annual attack count, and more frequent colchicine-resistant cases. Although E148Q is considered as a polymorphism in some populations, it was identified as a disease-causing mutation in our cohort. Secondary amyloidosis is still happening in adults however, it is extremely rare among children, presumably due to increased awareness, tight control, and the availability of anti-IL1 agents in colchicine-resistant cases.

Correlation genotype-phenotype: MEFV gene mutations and Moroccan patients with rheumatoid arthritis.

Introductionrheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting the joints. Arthritic disorders are associated with mutations of the Mediterranean fever (MEFV) gene. The aim of this study is to show whether MEFV mutations will be involved in the pathogenesis of RA, to explore the frequency of these mutations and to study the genotype-phenotype correlation between mutations in this gene and a cohort of Moroccan patients with rheumatoid arthritis (RA).Methodsthe present study included 100 patients with RA and 200 control group (CG) who were unrelated individuals from the same ethnic. All patients were tested for auto-antibodies: cyclic citrullinated peptide (ACPA/anti-CCP2), rheumatoid factor (RF) and were analyzed by Sanger Sequencing of the 2 and 10 exons of MEFV gene (hot-spot according to the literature).Resultswe detected 13 missense variants already MEFV gene mutation reported in the literature (S154T, G222A, G230L, L611H, L695A, M694V, I720M, A737L, P758S, L709A, T732A, G687A and P743L). Carrier rates of MEFV gene mutations were 24/100 (24%) for the RA group and 4/200 (4%) for CG. In the RA group, we observed that no man has presented with MEFV mutation. In the RA group, while gender, BMI, RF and ACPA were significantly higher in the mutation carrier group than those of the non-carrier group (p<0.01). The level of C-reactive protein and HAQ were slightly elevated in the carrier group but not significant. No other significant differences were observed between patients with MEFV mutations and those without MEFV mutations.Conclusionthe results of this study suggest that MEFV gene mutations appear to be an aggravating factor severity of RA and consequently, patients with RA might be screened for MEFV gene mutations in countries where FMF is frequent. We report also that our study is the first one in our country Morocco.

The analysis of genotype-phenotype correlation in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting with phenotypic heterogeneity. It is a clinically diagnosed disease supported by Mediterranean fever gene mutation analysis. This medical record review study aimed to make a new interpretation of clinical features in FMF patients by grouping genetic results based on the classification proposed by the Eurofever/ Paediatric Rheumatology International Trials Organisation. The medical charts of pediatric FMF patients who were diagnosed and followed up regularly at the two pediatric rheumatology units were reviewed. Genetic analysis results were classified as confirmatory and nonconfirmatory as defined in the new Eurofever/ Paediatric Rheumatology International Trials Organisation classification criteria, and they were compared with clinical findings. A total of 216 FMF patients were involved in the study. Group 1 was composed of 133 (61.6%) patients with a confirmatory mutation and group 2 included 83 (38.4%) patients with a nonconfirmatory mutation. All clinical findings were compared, and in terms of fever (P = 0.027), abdominal pain (P = 0.016), arthritis (P = 0.008) and erysipelas-like erythema (ELE; P = 0.003) incidence, there was a significant difference between the two groups. The most common Mediterranean fever gene mutation patterns were homozygous (33.8%) and heterozygous (17.1%) mutations of M694V. The frequency of arthritis and ELE in patients with M694V homozygous mutations was significantly higher than in the other patients (P = 0.002 and P <0.001, respectively). The most frequently observed clinical features of FMF (i.e., fever and abdominal pain) are both observed in patients with confirmatory and nonconfirmatory mutations, ELE and arthritis are more commonly observed in patients with confirmatory mutations.

Evaluation of the Clinical Effects and Frequency of MEFV Gene Mutation in Patients with Inflammatory Bowel Disease.

Background The clinical and pathological features of inflammatory bowel disease (IBD) and Familial Mediterranean Fever (FMF) are similar. Objective Here, the frequency of Mediterranean Fever (MEFV) gene mutation and its effect on the outcome of IBD were evaluated. Methods DNA sequence analysis detected the variants on the MEFV gene in patients with IBD. The relationship between mutations and the need for steroids, immunomodulators, biologics, and surgery was assessed. Results We evaluated 100 patients with IBD (55 with ulcerative colitis (UC) and 45 with Crohn's disease (CD)) and 60 healthy individuals as controls. The frequency of MEFV gene mutation was 26.7% (n = 12) and 14.5% (n = 8) for UC and CD, respectively. No relationship was found between MEFV gene mutation and the need for steroids, immunomodulators, and biologics (p = 0.446; p = 0.708; p > 0.999, resp.); however, in UC, the need for surgery in those with mutation (p = 0.018) and E148Q mutation alone was significant (p = 0.037). Conclusion The rate of MEFV gene mutations was high in patients with UC who required surgery. These patients have frequent and severe attacks, indicating that the mutations are related to disease severity. MEFV mutation as a modifier factor of IBD should be considered.

Spectrum of Mutations of Familial Mediterranean Fever Gene by Whole Sequencing Method in Iranian Patients

Background: Familial Mediterranean fever (FMF) is the most common type of periodic fever syndrome. The disease is most prevalent in the western Mediterranean population, but today it is widespread in the world due to the large ethnic migrations of Turks, Jews, Arabs and Armenians. The MEFV gene is the only gene known to be associated with the disease. Objectives: The aim of this study was to characterize pathogenic mutations in patients with typical FMF symptoms by sequencing the entire MEFV gene. Methods: This is a descriptive-analytical study that was performed during ten years from 2009 to 2019. On 252 patients after clinical diagnosis based on existing criteria to determine mutations referred to Tehran Medical Genetics Laboratory and the whole sequencing method for MEFV gene was used to determine mutations. Results: Out of 252 patients, 143 (56.7%) had pathogenic variants, and 109 (43.3%) had no variants reported as pathogenic mutations. Variants were identified as fallow: (1) 8.7% as homozygous; (2) 22.2% as compound heterozygous; (3) 25.7% as heterozygous. The most common variants were M694V (c.2080A&gt;G) and E148Q (c.442G&gt;C). Conclusions: This study showed that the age of onset of the disease was in the first and second decades of life amongst our patients and the most common complaints of patients were periodic fever and abdominal pain. The most frequent allele was M694V (c.2080A&gt;G) followed by E148Q (c.442G&gt;C) allele.

MEFV mutation frequencies in a Turkish cohort with low prevalence of familial Mediterranean fever

Background/aimFamilial Mediterranean fever (FMF) is a genetically recessive autoinflammatory disease caused by mutations in the Mediterranean fever (MEFV) gene. The aim of this study was to investigate the frequencies of the most common MEFV mutations among a sample of healthy individuals from the Havsa population of European Turkey, where FMF is less prevalent compared to Asian Turkey.Materials and methodsThe study group consisted of 263 unrelated healthy adults. All of the participants were analyzed for the M694V, V726A, M680I, and E148Q mutations in the MEFV gene.ResultsIn total, 25 of the 263 individuals carried MEFV mutations (9.5%). The observed allele frequencies were 1.5% for M694V (95% confidence interval [CI] 0.5-2.5), 2.6% for E148Q (95% CI 1.6-3.9), 0.5% for M680I (95% CI 0.0-1.1), and 0.0% for V726A. The frequencies of the M694V, M680I, and E148Q mutations were not significantly different from allele frequencies (approximately 20%) determined for other regions of Turkey where FMF is more prevalent.ConclusionThese data suggest that the positivity of the MEFV gene mutation tests have lower predictive value in a population with low FMF prevalence.

Assessment of mean platelet volume and aortic intima media thickness in pediatric familial Mediterranean fever: as early markers of atherosclerosis.

Familial Mediterranean fever is the most common auto-inflammatory disease in childhood. The aim of present study is to assess whether familial Mediterranean fever increases the risk of premature atherosclerosis. It is a case-control prospective study. The study included 32 patients in attack-free period and 22 healthy children who did not have any chronic disease. Demographic features, clinical findings, response to colchicine therapy, Mediterranean Fever gene mutations were recorded in familial Mediterranean fever group. Mean platelet volume and intima-media thickness were evaluated as a possible marker of early onset atherosclerosis. Intima media thickness of abdominal aorta and common carotid arteries with color Doppler ultrasound, mean platelet volume and acute phase reactants were measured in both groups. No significant difference was documented between the patient and control groups regarding the intima-media thickness (p>0, 05). Familial Mediterranean fever patients had significantly higher mean platelet volume values compared with the controls (8.35±1.0 vs. 7.79±0.78 fl, p=0.026). Intima media thickness and mean platelet volume values of familial Mediterranean fever patients were not correlated with lipid profiles, inflammatory markers. The present study found out no evidence that intima media thickness of abdominal aorta and common carotid arteries in familial Mediterranean fever patients could predict early atherosclerosis. However, mean platelet volume value was found higher in children with familial Mediterranean fever. Mean platelet volume may be useful marker to show premature atherosclerosis in familial Mediterranean fever.

Evaluation of Clinical, Genetic and Treatment-Related Characteristics in FMF Patients by Gender Distribution

The aim of this study is to investigate the differences between males and females in clinical findings, hereditary characteristics, treatment responses and pathogen Mediterranean fever (MEFV) gene phenotype frequencies in FMF patients. The data of 105 patients (70 females, 35 males) whose charts were available for all research data were evaluated. While evaluating the clinical findings; The age of attack onset, attack character, dominant attack location, presence of recurrent fever, appendectomy history and family history were evaluated. the response to colchicine treatment was questioned. The phenotype frequencies of the pathogen variations in the MEFV gene were determined. The frequency of individuals with typical attack character was 71.4% in women and 82.9% in men. The frequency of the predominant attack localization with peritoneum was 90% in women and 88.6% in men. The proportion of those with colchicine response was 92.8% and 85.7% in women and men, respectively. The phenotype frequencies of pathogen MEFV gene mutations were 62.7% and 88.6% for M694V (p=0.006), 22.4% and 14.3% (p=0.328) for V726A, 20.9% for M680I in women and men, respectively, and 22.9% (p = 0.819) and 14.9% and 14.3% (p=0.931) for E148Q. Clinical findings and treatment responses are not different in individuals with FMF disease. The frequency of the M694Vmutation, which has high penetration and is associated with important complications such as amyloidosis, is higher in men. There is a need for studies to evaluate FMF activity according to gender distribution.