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Objectives: This study aims to analyze the growth parameters in children with familial Mediterranean fever (FMF) according to disease characteristics including genotype and disease severity by a recently validated tool in relatively more patients. Patients and methods: This retrospective study included 126 patients with FMF (70 males, 56 females; mean age 7.3±3.6 years; range, 4.1 to 18 years). MEditerranean FeVer (MEFV) gene analysis was performed with a molecular diagnostics tool by using a next-generation sequencing platform. Disease severity was determined for the first visit by the validated tool in children, international severity scoring system for FMF. Growth parameters including weight and height were investigated after standard deviation (SD) scores were calculated by anthropometric references in Turkish children. Results: Median follow-up duration was 74.7 months (range, 7.5 to 169 months). Ninety-three patients (73.8%) had at least one M694V mutation in MEFV gene. Six patients (4.8%) had severe disease, 58 (46%) had intermediate severity, and 62 (49.2%) had mild disease. Mean height SD score was significantly lower at last visit than before colchicine treatment. Initial and last height and weight SD scores were lower in patients with at least one M694V mutation than those without. However, the difference was statistically significant for only initial height SD score. We also found statistically significant lower initial height, final height, and weight SD scores in patients with intermediate severity-severe disease activity than mild disease. Conclusion: We advise physicians to score disease severity prospectively and pay attention to patients with intermediate severity-severe disease to avoid growth disturbances. © 2019 Turkish League Against Rheumatism.

WOS: 000463722100007, PubMed ID: 30489254, Objective: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. Most of the identified disease-causing mutations are located on exon 10. As the number of studies about the effect of the exonal location of the mutation and its phenotypic expression is limited, we aimed to investigate whether the exonic location of the Mediterranean fever (MEFV) mutation has an effect on the clinical manifestation in patients with FMF. Methods: Study population was derived from the main FMF registry that included 2246 patients from 15 different rheumatology clinics. We categorized the mutations according to their exon locations and retrieved the clinical and demographic information from the database. Results: Patients having the MEFV mutations on exon 2 or 10 (n: 1526) were divided into three subgroups according to the location of the MEFV mutations: Group 1 (exon 2 mutations), Group 2 (exon 10 mutations), and Group 3 (both exon 2 and exon 10 mutations). Group 2 patients were of a significantly younger age at onset, and erysipel-like erythema, arthritis, amyloidosis, and a family history of FMF were more common in this group. Conclusion: Patients with FMF and exon 10 mutations show more severe clinical symptoms and outcome. Exon 2 mutations tend to have a better outcome.

PubMedID: 29314707 Aim: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. One of the common characteristics of this disease is its young age predominance. Nearly 90% of patients experience disease flares during early adult age periods. Currently there are limited data for the comparison of early versus late onset FMF and therefore the primary aim of this study was to investigate these two subsets with regard to their certain demographic, clinical and genetic differences. Methods: Early (? 20 years, Group 1) and late (> 20 years, Group 2) onset FMF patients were identified from the national FMF registry that involves 2246 patients from 15 adult rheumatology clinics located in different geographical areas of Turkey. Results: Of the 2246 patients, 1633 (72.7%) were aged ? 20 years old (Group 1) and the remaining 613 were older than 20 years (Group 2). Delay in diagnosis was longer in Group 1 and fever, peritonitis, pleuritis, erysipelas- like erythema (ELE), arthritis, family history of FMF and amyloidosis were more common in Group 1. On the other hand, sex distribution, rates of amyloidosis, vasculitis and kidney failure were not different between the groups. Among patients with available genotypes, homozygous and heterozygous M694V mutations were significantly higher and heterozygous E148Q mutation was significantly lower in Group 1 compared to Group 2. Conclusion: Patients with FMF whose symptoms start before 20 years of age seem to have severe symptoms and M694V mutation may be responsible for the early expression of the disease. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

WOS: 000333263500025, PubMed ID: 24369413, Methods. Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. Results. There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (s.d. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). Conclusion. In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

OBJECTIVE: The aim of this study was to perform a systematic review of the relevant literature aiming to assess the role of MEFV mutations on FMF-associated PAN. MATERIAL and METHODS: We conducted a comprehensive review of the literature with an attempt to analyze cumulated data regarding the role of MEFV mutations in the development of FMFassociated PAN. RESULTS: We found a total of 96 cases with FMF and PAN. MEFV mutations were available only in 28 patients of whom 26 have been reported from Turkey. Twenty-five (89 %) of the 28 patients had at least one M694V allele and 13 (46%) of them had the homozygous M694V genotype. CONCLUSION: Since M694V is accepted to be associated with more severe inflammation as compared to other mutations, one can speculate that this enhanced inflammation may predispose to PAN and MEFV mutations and probably contribute to the risk of developing PAN in areas where FMF is endemic. In addition, MEFV mutations, particularly M694V, might be searched in patients from certain ethnic groups, especially in young patients having PAN without any predisposing disease.

BACKGROUND: Familial Mediterranean fever (FMF) is autosomal recessive disease that affects people from Mediterranean region, Europe and Japan. Its gene (Mediterranean fever [MEFV]) has more than 100 mostly non-sense mutations. OBJECTIVES: The objective of the following study is to provide some phenotype-genotype correlates in FMF by categorizing the Egyptian FMF cases from Delta governorates after analysis of the four most common mutations of MEFV gene (M680I, M694I, M694V, V726A). SUBJECTS AND METHODS: Clinically, suspected FMF cases using Tel-Hashomer criteria were enrolled in the study. Cases were referred to Mansoura University Children's Hospital that serves most of the most middle Delta governorates, in the period from 2006 to 2011. Subjects included 282 males and 144 females, mean age of onset 9.3 ± 2.2 years. All cases were analyzed for these mutations using amplification refractory mutation system based on the polymerase chain reaction technique. Five FMF patients agreed to undergo renal biopsy to check for development of amyloidosis. Analysis of data was carried out using SPSS (SPSS, Inc., Chicago, IL, USA). RESULTS: Mutation was found in 521 out of 852 studies alleles, the most frequent is M694V (35.4%) followed by M694I, V726A and M680I. 11 cases were homozygous; 7 M694V, 3 M680I and only one M694I case. Severe abdominal pain occurred in 31 (7.28%) but severe arthritis in 103 cases (24.2%). Strong association was found between arthritis and homozygous mutant compared with single and double heterozygous (72.7% vs. 33.3% and 20.24%, P < 0.001). Four amyloid cases were M694V positive. CONCLUSION: M694V allele is the most common among Egyptian FMF especially those with amyloidosis. We recommend routine check for amyloidosis in FMF cases to statistically validate this link.