Recurrent Synovitis of Hip and MEFV Gene Related Arthritis in Children

Abstract Background: Familial Mediterranean fever (FMF) is an autosomal recessive inherited auto inflammatory disorder. Arthritis is the presenting finding of FMF in some patients, and sometimes it remains as the major manifestation of the disorder. This study reports three non-FMF patients with heterozygous MEFV gene mutations and an extraordinary arthritis as a recurrent synovitis of hip (RSH) Methods: During 16-years from 2003 to 2019 at pediatric rheumatologic clinic among 195 recorded files, 3 patients with diagnosis of recurrent synovitis of hip (RSH) were reviewed thoroughly. Peripheral blood was collected from patients and the samples were screened for the 12 common MEFV gene pathogenic variants. Results: This study included three patients, two female and one male with relapsing arthritis that has been located on hip joints as a sole manifestation and pathologic findings of MEFV mutations as follow: A744S, V726A, and R761H. Conclusion: On the basis of possible role of MEFV gene in different rheumatic disease RSH could be considered as a MEFV gene related arthritis. Key words: FMF, MEFV gene, Recurrent synovitis of hip in children

Recurrent Synovitis of Hip and MEFV Gene Related Arthritis in Children

10.21203/rs.3.rs-22325/v1 ◽

2020 ◽

Author(s):

Farhad Salehzadeh ◽

Mehrdad Mirzarahimi

Keyword(s):

Rheumatic Disease ◽

Peripheral Blood ◽

Mefv Gene ◽

Gene Mutations ◽

Mediterranean Area ◽

Hip Joints ◽

Mefv Mutations ◽

Pathogenic Variants ◽

Pathologic Findings

Abstract Background : Recurrent and relapsing arthritis has been proposed to describe a group of arthritis with recurring and periodic nature, in which the joints are intermittently involved. This study reports three non-FMF patients with heterozygous MEFV gene mutations and an extraordinary arthritis as a recurrent synovitis of hip (RSH) Methods : During 16-years from 2003 to 2019 at pediatric rheumatologic clinic among 195 recorded files with chronic oligoarthritis, 3 patients with diagnosis of recurrent synovitis of hip (RSH) were reviewed thoroughly. Peripheral blood was collected from patients and the samples were screened for the 12 common MEFV gene pathogenic variants. Results: This study included three patients, two female and one male with relapsing idiopathic arthritis that has been located on hip joints as a sole manifestation and pathologic findings of MEFV mutations as follow: A744S, V726A, and R761H. Conclusion : On the basis of possible role of MEFV gene in different rheumatic disease, MEFV gene related arthritis may be considered as a background of RSH particularly in Mediterranean area.

The Frequency of Familial Mediterranean Fever Gene Mutations and the Correlations between Phenotype and Genotype in Turkish Children

Asian Journal of Pediatric Research ◽

10.9734/ajpr/2020/v4i230145 ◽

2020 ◽

pp. 20-26

Author(s):

Hakan Erdogan ◽

Ayse Cavidan Sonkur ◽

Orhan Görükmez ◽

Ayse Erdogan ◽

Dilek Damla Saymazlar ◽

...

Keyword(s):

Mutation Screening ◽

Mefv Gene ◽

Gene Mutations ◽

Retrospective Case ◽

Turkish Children ◽

Pathogenic Variants ◽

Frequent Mutations ◽

Training And Research ◽

Aim: Familial Mediterranian Fever is an autosomal recessive disease characterized by recurrent inflammatory attacks of serosal membranes. The aim of the current study was to determine the frequency of the Mediterranean fever (MEFV) gene pathogenic variants in 158 children (78 male, 80 female) diagnosed with Familial Mediterranean Fever (FMF) and to compare the phenotype-genotype correlation. Methods: In our retrospective case-control study, 158 FMF patients (78 males, 80 females) who were diagnosed with MEFV gene mutation in Bursa Yuksek Ihtisas Training and Research Hospital, Department of Pediatrics between January 2018 and June 2019 were included in the study. Mutation screening of the MEFV gene was performed for 12 mutations and the 8 most common mutations were taken into the study. Results: Abdominal pain (77.8%), fever (74%) and arthralgia (46.2%) were the most prevalent clinical features in our patients. The most frequent mutations were M694V, E148Q, V726A, M680I and P369S. In cases with M694 mutation, it was noted that the incidence of arthritis was 2.5 times, appendectomy frequency 3.1 times higher, and early diagnosis probability 3.2 times higher. The frequency of chest pain was 2.9 times higher in the M680I mutation, and the frequency of arthralgia was 2.2 times higher in the P369S mutation. Conclusion: Patient’s mutations in FMF patients are important for clinical expectations, and some mutations such as P369S are not as innocent as expected. However, reevaluation of phenotypes of mutations that are rare with more patients will be significant.

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

Autoimmune Diseases ◽

10.1155/2014/238931 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3 ◽

Cited By ~ 3

Author(s):

Farhad Salehzadeh ◽

Ozra Yasrebi ◽

Mahsa Hosseini Khotbesara ◽

Maryam Hosseini Khotbesara

Keyword(s):

Inflammatory Process ◽

Mefv Gene ◽

Gene Mutations ◽

The Other ◽

Blurred Vision ◽

Mefv Mutations ◽

Auto Inflammatory Disease ◽

Mediterranean Fever ◽

Positive Results

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.

Spectrum of MEFV Variants and Genotypes among Clinically Diagnosed FMF Patients from Southern Lebanon

Medical Sciences ◽

10.3390/medsci8030035 ◽

2020 ◽

Vol 8 (3) ◽

pp. 35

Author(s):

Ali El Roz ◽

Ghassan Ghssein ◽

Batoul Khalaf ◽

Taher Fardoun ◽

José-Noel Ibrahim

Keyword(s):

Autosomal Recessive ◽

Mefv Gene ◽

Allele Frequencies ◽

Molecular Testing ◽

Compound Heterozygous ◽

Pathogenic Variants ◽

South Lebanon ◽

Auto Inflammatory Disease ◽

Mediterranean Fever ◽

The Mean

Background: Familial Mediterranean Fever (FMF) is an autosomal recessive auto-inflammatory disease characterized by pathogenic variants in the MEFV gene, with allele frequencies greatly varying between countries, populations and ethnic groups. Materials and methods: In order to analyze the spectrum of MEFV variants and genotypes among clinically diagnosed FMF patients from South Lebanon, data were collected from 332 participants and 23 MEFV variants were screened using a Real-Time PCR Kit. Results: The mean age at symptom onset was 17.31 ± 13.82 years. The most prevalent symptoms were abdominal pain, fever and myalgia. MEFV molecular analysis showed that 111 patients (63.79%) were heterozygous, 16 (9.20%) were homozygous, and 47 (27.01%) carried two variants or more. E148Q was the most encountered variant among heterozygous subjects. E148Q/M694V was the most frequent in the compound heterozygous/complex genotype group, while M694I was the most common among homozygous patients. Regarding allele frequencies, M694V was the most common variant (20.7%), followed by E148Q (17.1%), V726A (15.7%) and M694I (13.2%). Conclusion: The high percentage of heterozygous patients clinically diagnosed as FMF highlights the pseudo-dominant transmission of the disease in Lebanon and emphasizes the importance of molecular testing for a more accurate diagnosis and better management and treatment of FMF.

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

Biologia ◽

10.2478/s11756-009-0047-1 ◽

2009 ◽

Vol 64 (2) ◽

Cited By ~ 4

Author(s):

Binnur Koksal ◽

Naim Nur ◽

Musa Sari ◽

Ferhan Candan ◽

Mursit Acemoglu ◽

...

Keyword(s):

Severe Disease ◽

Mefv Gene ◽

Point Mutations ◽

Gene Mutations ◽

Homozygous Mutation ◽

Frequent Mutation ◽

Mefv Mutations ◽

Wide Range ◽

AbstractFamilial 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.

FAMILIAL MEDITERRANEAN FEVER: ASSESSING THE OVERALL CLINICAL IMPACT AND FORMULATING TREATMENT PLANS

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2019.027 ◽

2019 ◽

Vol 11 (1) ◽

pp. e2019027 ◽

Cited By ~ 8

Author(s):

Donato Rigante ◽

Raffaele Manna

Keyword(s):

Therapeutic Option ◽

Interleukin 1 ◽

Mefv Gene ◽

Clinical Signs ◽

Gene Mutations ◽

Recessive Trait ◽

Aa Amyloidosis ◽

Mefv Mutations ◽

Recurrent self-limited attacks of fever and short-lived inflammation in the serosal membranes, joints and skin are the leading features of familial Mediterranean fever (FMF), the most common autoinflammatory disorder in the world, transmitted as autosomal recessive trait caused by MEFV gene mutations. Their consequence is an abnormal function of pyrin, a natural repressor of inflammation, apoptosis and release of cytokines. FMF-related mutant pyrins are hypophosphorylated following RhoA GTPases’ impaired activity and show a propensity to relapsing uncontrolled systemic inflammation with inappropriate response to inflammatory stimuli and leukocyte spread to serosal membranes, joints or skin. Typical FMF phenotype 1 consists of brief episodes of inflammation and serositis, synovitis, and/or erysipelas-like eruption, whereas phenotype 2 is defined by reactive amyloid-associated (AA) amyloidosis, which is the most ominous complication of FMF, in otherwise asymptomatic individuals. Furthermore, FMF phenotype 3 is referred to the presence of two MEFV mutations with neither clinical signs of FMF, nor AA amyloidosis. The influence of epigenetic and/or environmental factors can contribute to the variable penetrance and phenotypic heterogeneity of FMF. Colchicine, a tricyclic alkaloid with anti-microtubule and anti-inflammatory properties, is the bedrock of FMF management: daily administration of colchicine prevents the recurrence of FMF attacks and the development of secondary AA amyloidosis. Many recent studies have also shown that anti-interleukin-1 treatment is actually the best therapeutic option for FMF patients nonresponsive or intolerant to colchicine. This review aims to catch readers’ attention on the clinical diversity of phenotypes, differential diagnosis, and management of patients with FMF.

AB0782 MONOARTHRITIS: PROBABLE OUTCOMES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3630 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1417.1-1417

Author(s):

M. Osipyan ◽

M. Efraimidou ◽

V. Vardanyan ◽

K. Ginosyan

Keyword(s):

Joint Distribution ◽

Complete Blood Count ◽

Mefv Gene ◽

Baseline Data ◽

Mefv Mutations ◽

Appropriate Treatment ◽

Number Of Patients ◽

Female Predominance ◽

Mediterranean Fever ◽

Systemic Manifestations

Background:Numerous joint disorders initially produce swelling in a single joint and new onset monoartritis will probably further lead to the involvement of other joint groups and development of extraarticular manifestations. It is essential to take a proper diagnostic approach for organizing appropriate treatment and lowering possibility of disease progression.Objectives:The aim of this study was to investigate joint distribution, determine rheumatological diseases of patients with acute monoarthritis and reveal the development of further systemic manifestations.Methods:100 patients (age 18-75 years) with clinically apparent monoarthritis of less than 6 weeks duration were included in the study. Criteria of exclusion were infection, trauma and crystal induced arthritis. Joint distribution, presence of systemic manifestations and development of chronic inflammatory rheumatic disease were evaluated. Presence of arthritis was proved with help of ultrasound examination. Complete blood count, ESR, CRP, RF, anti-CCP; HLAB27; MEFV mutations and X-ray of swollen joint were performed for all patients. Temperature was also measured.Results:Mean age of patients with acute monoarthritis was 46±13 years. Female predominance was noted (61%). 71% of patients had elevated ESR, 69%- CRP. In 24% of cases homozygous or heterozygous mutations of MEFV gene were revealed. 21% of patients had positive RF and 18% - anti-CCP. 11% patients carried HLA-B27 antigen. 28% of examined patients had subfebril fever. Hepatosplenomegaly was determined in 16%, uveitis in 5%, psoriatic plaque in 4%, interstitial pneumonia in 2% of casesAt the baseline 82 patients were diagnosed with rheumatologically disease. Baseline data is shown in the Table 1 bellow.Table 1.Baseline dataDiagnosis Number of patientsFMF23Osteoarthritis (reactive synovitis)16Rheumatoid arthritis15Reactive arthritis10Ankylosing spondylitis6Psoriatic arthritis4SLE3Schonleyn-Henoch purpura2Sarcoidosis2Behcet diseases1Conclusion:In this study monoarhtritis in majority of cases underlies FMF. Though FMF is not considered as a frequent cause of acute monoarthritis, more attention should be paid on this pathology in focus of monoarthritis, especially in specific for FMF region. Further follow up of acute monoarthritis progression is needed.References:[1]A. Becker, J. Daily, K. Pohlgeers. Acute Monoarthritis: Diagnosis in Adults.Am Fam Physician 2016; 94(10): 810-816[2]S. Camacho-Lovillo, A. García-Martínez. Arthritis as presentation of familial Mediterranean fever. An Pediatr (Barc). 2015; 83(2):130. DOI: 10.1016/j.anpede.2015.07.007[3]J. Ellis. Acute monoarthritis. JAAPA. 2019, 32(3):25-31. doi: 0.1097/01.JAA.0000553379.52389.ebDisclosure of Interests:None declared

Familial Mediterranean fever-associated mutation pyrin E148Q as a potential risk factor for multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458512437813 ◽

2012 ◽

Vol 18 (9) ◽

pp. 1229-1238 ◽

Cited By ~ 11

Author(s):

T Kümpfel ◽

L-A Gerdes ◽

T Wacker ◽

A Blaschek ◽

J Havla ◽

...

Keyword(s):

Multiple Sclerosis ◽

Risk Factor ◽

Mefv Gene ◽

German Population ◽

Gene Group ◽

Mefv Mutations ◽

Mediterranean Fever ◽

Group 2 ◽

Group 1

Background: Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease caused by mutations in the MEFV gene and characterized by recurrent febrile polyserositis. A possible association of FMF and multiple sclerosis (MS) has been suggested in cohorts from Turkey and Israel. Objective: The objective of this study was to investigate the prevalence of MEFV mutations in subjects with MS and in controls in Germany. Methods: One-hundred and fifty seven MS patients with at least one symptom or without symptoms suggestive of FMF from our outpatient clinic were investigated for mutations in exons 2, 3, and 10 of the MEFV gene (group 1). 260 independent MS patients (group 2) and 400 unrelated Caucasian controls (group 3) were screened selectively for the low-penetrance pyrin mutations E148Q and K695R Results: In group 1, 19 MS patients (12.1%) tested positive for a mutation in the MEFV gene, mainly the E148Q ( n=7) substitution. Fifteen of the 19 mutation-positive individuals reported at least one symptom suggestive of FMF. In three cases, we could identify additional family members with MS. In these pedigrees, the E148Q exchange co-segregated with MS ( p=0.026). Frequencies of the pyrin E148Q and K695R mutations were not statistically different between MS group 2 and controls but they occurred with a surprisingly high frequency in the German population. Conclusion: The MEFV gene appears to be another immunologically relevant gene locus which contributes to MS susceptibility. In particular, the pyrin E148Q mutation, which co-segregated with disease in three MS families, is a promising candidate risk factor for MS that should be further explored in larger studies.

MEFV gene mutations in Iranian patients with familial mediterranean fever (FMF)

The American Journal of Gastroenterology ◽

10.1016/s0002-9270(03)00980-8 ◽

2003 ◽

Vol 98 (9) ◽

pp. S72-S73 ◽

Cited By ~ 1

Author(s):

M ZALI

Keyword(s):

Mefv Gene ◽

Gene Mutations ◽

Mediterranean Fever ◽

Iranian Patients

Common Mediterranean Fever (MEFV) Gene Mutations Associated with Ankylosing Spondylitis in Turkish Population

Disease Markers ◽

10.1155/2012/890214 ◽

2012 ◽

Vol 33 (3) ◽

pp. 113-118 ◽

Cited By ~ 9

Author(s):

Serbulent Yigit ◽

Ahmet Inanir ◽

Nevin Karakus ◽

Esra Kesici ◽

Nihan Bozkurt

Keyword(s):

Ankylosing Spondylitis ◽

Mefv Gene ◽

Gene Mutations ◽

Turkish Population ◽

M694v Mutation ◽

Significant Difference ◽

Mediterranean Fever ◽

Genomic Dnas ◽

Polymerase Chain ◽

Turkish Patients

Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease. Mediterranean fever (MEFV) gene, which has already been identified as being responsible for familial Mediterranean fever (FMF), is also a suspicious gene for AS because of the clinical association of these two diseases. The aim of this study was to explore the frequency and clinical significance ofMEFVgene mutations (M694V, M680I, V726A, E148Q and P369S) in a cohort of Turkish patients with AS. Genomic DNAs of 103 AS patients and 120 controls were isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. There was a statistically significant difference of theMEFVgene mutation carrier rates between AS patients and healthy controls (p= 0.004, OR: 2.5, 95% CI: 1.32–4.76). This association was also observed in allele frequencies (p= 0.005, OR: 2.3, 95% CI: 1.27–4.2). A relatively higher frequency was observed for M694V mutation in AS patients than controls (10.7% versus 4.2% ,p= 0.060). There were no significant differences between MEFV mutation carriers and non-carriers with respect to the clinical and demographic characteristics. The results of this study suggest thatMEFVgene mutations are positively associated with a predisposition to develop AS.