The Assessment of Selected miRNA Profile in Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is the most prevalent autoinflammatory disease. Typical findings are recurrent fever attacks with serositis, skin rash, and synovitis. FMF is caused by mutations in the MEFV gene, encoding pyrin protein. Pyrin functions in innate immunity and triggers inflammation via inflammatory mediators’ production and acts as the primary regulatory component of the inflammasome. On the other hand, various miRNAs play crucial roles in the pathogenesis of different types of cancers and immune-related and neurodegenerative diseases. However, their association with FMF is still unclear. Therefore, in this study, we assessed the roles of selected thirteen miRNAs associated with immune functions. We recruited genetically diagnosed 28 FMF patients and 28 healthy individuals. The expression profiling of the miRNAs was determined by qRT-PCR and normalized to SNORD61. Our analysis revealed that miR-34a-5p, miR-142-3p, miR-216a-5p, miR-340-5p, miR-429, and miR-582-5p were upregulated, whereas miR-107, miR-569, and miR-1304-5p were downregulated in the FMF patients. Among them, miR-107 was found to be the most remarkable in M694V homozygous mutants compared to other homozygous mutants. During clinical follow-up of the patients with M694V mutation, which is closely related to amyloidosis, evaluation of mir-107 expression might be crucial and suggestive. Our results showed that miRNAs might serve a function in the pathogenesis of FMF. Further studies may provide novel and effective diagnostic and therapeutic agents that target examined miRNAs. Targeting miRNAs in FMF seems to be promising and may yield a new generation of rational therapeutics and diagnostic or monitoring tools enabling FMF treatment.

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Differentiating children with familial Mediterranean fever from other recurrent fever syndromes: The utility of new Eurofever/PRINTO classification criteria

Archives of Rheumatology ◽

10.46497/archrheumatol.2021.8616 ◽

2021 ◽

Vol 36 (4) ◽

pp. 493-498

Author(s):

Rabia Miray Kışla Ekinci ◽

Sibel Balcı ◽

Ahmet Hakan Erol ◽

Dilek Karagöz ◽

Derya Ufuk Altıntaş ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Sensitivity And Specificity ◽

Mefv Gene ◽

Classification Criteria ◽

Recurrent Fever ◽

Control Group ◽

Mevalonate Kinase Deficiency ◽

Cross Sectional ◽

M694v Mutation ◽

Mediterranean Fever

Objectives: In this study, we aimed to investigate the performance of Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria in pediatric patients with familial Mediterranean fever (FMF). Patients and methods:This retrospective, cross-sectional study included a total of 130 pediatric FMF patients (67 males, 63 females; mean age: 12.4±3.6 years; range, 2.5 to 17.7 years) with at least one M694V mutation in MEFV gene between July 2010 and July 2019. Demographic features and disease characteristics were recorded. The control group was consisted of 41 patients (19 males, 22 females; mean age: 7.8±4.0 years; range, 2.1 to 17.8 years) with other hereditary autoinflammatory diseases (AIDs), including periodic fevers with aphthous stomatitis, pharyngitis, and adenitis syndrome (n=30), mevalonate kinase deficiency (n=9), and tumor necrosis factor receptor-associated periodic syndrome (n=2). Sensitivity and specificity of the Eurofever/PRINTO classification criteria were calculated. Results: The sensitivity and specificity were 97.7% and 56.1% for Yalcinkaya-Ozen criteria, respectively and 93.1% and 90.2% for Tel Hashomer criteria, respectively. The Eurofever/PRINTO classification criteria reached a sensitivity and specificity of 94.6% and 82.9% and 93.1% and 80.5%, respectively, when genetic plus clinical criteria and clinical-only criteria were applied. Conclusion: The Eurofever/PRINTO classification criteria have a comparable sensitivity for avoidance of FMF underdiagnosis in childhood. The Yalcinkaya-Ozen criteria have the highest sensitivity without a significant specificity. The Tel Hashomer criteria and Eurofever/PRINTO classification criteria were superior to Yalcinkaya-Ozen criteria to differentiate FMF from other AIDs, thus leading to less complications relevant to underdiagnosis of other AIDs.

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A new MEFV gene mutation in an Iranian patient with familial Mediterranean fever

Reumatismo ◽

10.4081/reumatismo.2019.1141 ◽

2019 ◽

Vol 71 (2) ◽

pp. 85-87

Author(s):

S. Farjadian ◽

F. Bonatti ◽

A. Soriano ◽

M. Reina ◽

A. Adorni ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Mutational Analysis ◽

Novel Mutation ◽

Present Report ◽

Case Reports ◽

Mefv Gene ◽

Recurrent Fever ◽

Iranian Patient ◽

Mediterranean Fever ◽

Exon 10

Familial mediterranean fever (FMF) is an inherited autoinflammatory disorder characterized by recurrent episodes of fever and painful inflammation involving the intra-abdominal organs, the lungs and the joints, which is highly prevalent in specific ethnic groups including the Iranians. We report a 12-year-old boy from Iran, with a clinical history of recurrent fever. Based on the suggestive clinical data, mutational analysis revealed the presence of the novel c.1945C>T heterozygous variant in exon 10, which leads to a leucine to phenylalanine change at position 649 of the protein. The mutation was inherited from the mother. This novel mutation lies in exon 10 of the MEFV gene, which encodes for a domain called B30.2-SPRY, located in the C-terminal region of the pyrin protein and contains the most frequent mutations associated with FMF. The present report expands the spectrum of MEFV gene mutations associated with FMF. The uniqueness of this study, compared with other published case reports, consists in the new mutation found in the MEFV gene. In fact, new mutations in this gene are of high interest, in order to better understand the role of this gene in autoinflammation.

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Sacroiliitis and Polyarteritis Nodosa in a Patient with Familial Mediterranean Fever

Case Reports in Medicine ◽

10.1155/2016/5134546 ◽

2016 ◽

Vol 2016 ◽

pp. 1-3 ◽

Cited By ~ 3

Author(s):

Yunus Ugan ◽

Atalay Doğru ◽

Hüseyin Şencan ◽

Mehmet Şahin ◽

Şevket Ercan Tunç

Keyword(s):

Familial Mediterranean Fever ◽

Polyarteritis Nodosa ◽

Autosomal Recessive ◽

Mefv Gene ◽

Autosomal Recessive Inheritance ◽

Recurrent Fever ◽

Autoinflammatory Disorder ◽

Chromosome 16 ◽

Mediterranean Fever ◽

Schonlein Purpura

Familial Mediterranean fever (FMF) is an autoinflammatory disorder with autosomal recessive inheritance, characterized by recurrent fever and episodes of serositis. The condition is known to be caused by mutations in the MEFV (Mediterranean FeVer) gene, located in the short arm of chromosome 16. While more than 310 sequence variants in the MEFV gene have been described to date, the diagnosis is still established clinically. FMF may be accompanied by sacroiliitis and various forms of vasculitis. The most common forms of associated vasculitis are Henoch-Schonlein purpura and polyarteritis nodosa (PAN). We have presented here a fairly rare case of FMF, accompanied by both sacroiliitis and PAN.

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Comparison of Clinical and Demographic Features of FMF with Sacroiliitis Patients with FMF and Axial Spondyloarthritis Patients

Aktuelle Rheumatologie ◽

10.1055/a-1252-2190 ◽

2020 ◽

Author(s):

Esra Dilşat Bayrak ◽

Sukran Erten ◽

Orhan Kucuksahin ◽

Osman Ersoy

Keyword(s):

Inflammatory Markers ◽

Mefv Gene ◽

Gene Mutations ◽

Recurrent Fever ◽

Hla B27 ◽

M694v Mutation ◽

Genetic Features ◽

Mediterranean Fever ◽

Common Manifestation ◽

Musculoskeletal Involvement

Abstract Objectives Familial Mediterranean fever (FMF) is the most common autoinflammatory disease, characterised by recurrent fever and serositis attacks lasting 1–3 days. Musculoskeletal involvement is the second most common manifestation in FMF patients. Sacroiliitis is another musculoskeletal involvement; as there is no spinal involvement, this is called FMF with sacroiliitis. This study was designed to investigate the clinical, demographic and genetic features of FMF in sacroiliitis patients and to compare them with axial SpA and FMF patients. Materials and Methods Forty-two FMF with sacroiliitis patients, 100 axial SpA patients and 100 FMF patients were recruited, and their demographic characteristics were recorded. Evidence of sacroiliitis was confirmed by sacroiliac joint MRI, and patients were examined for arthritis and enthesitis. MEFV gene mutations, HLA B27 positivity and ESR and CRP results were compared. Results In the FMF with sacroiliitis group, the M694V mutation was detected in 59.5% of patients. FMF with sacroiliitis patients were largely (83.3%) negative for HLA B27. The frequency of enthesitis was similar between FMF with sacroiliitis and axial SpA, and the frequency of arthritis was higher in axial SpA patients. Inflammatory markers (ESR and CRP) were statistically higher in FMF with sacroiliitis patients compared with axial SpA and FMF patients. Conclusion When all three groups were compared, the M694V mutation was more common, HLA B27 was largely negative and inflammatory markers were higher in the FMF with sacroiliitis group. FMF should be included in the differential diagnosis of sacroiliitis for managing treatment correctly and preventing complications.

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An unusual presentation of familial Mediterranean fever with co-existing polyarteritis nodosa and acute post-streptococcal glomerulonephritis

10.22541/au.163769375.55781332/v1 ◽

2021 ◽

Author(s):

yesim ozdemir atikel ◽

Betul Emine Derinkuyu ◽

Sevcan Bakkaloğlu

Keyword(s):

Familial Mediterranean Fever ◽

Polyarteritis Nodosa ◽

Streptococcal Infection ◽

Mefv Gene ◽

Clinical Manifestations ◽

Unusual Presentation ◽

Mefv Mutation ◽

M694v Mutation ◽

Mediterranean Fever ◽

Post Streptococcal Glomerulonephritis

The homozygous M694V mutation in the MEFV gene may cause an augmented response to the streptococcal infection that plays a role in the development of APSGN and PAN. Both clinical manifestations may occur simultaneously after streptococcal infection in a child who is previously healthy but carries a MEFV mutation.

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AB1071 COEXISTENCE OF FAMILIAL MEDITERRANEAN FEVER WITH SPONDYLOARTHRITIS: CLINICAL CHARACTERISTIC AND TREATMENT OUTCOMES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4209 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1824.1-1825

Author(s):

T. Yüce İnel ◽

İ. Sari ◽

M. Birlik ◽

G. Can ◽

F. Onen

Keyword(s):

Familial Mediterranean Fever ◽

Treatment Outcomes ◽

Clinical Characteristics ◽

Mefv Gene ◽

Laboratory Data ◽

Gene Mutations ◽

Symptom Duration ◽

Hla B27 ◽

M694v Mutation ◽

Mediterranean Fever

Background:Studies indicate that there is an association with spondyloarthritis (SpA) and familial mediterranean fever (FMF) based on the following: 1) increased incidence of sacroiliitis in FMF, 2) MEFV gene mutations are significantly increased in ankylosing spondylitis (AS) and 3) both SpA and FMF show some common clinical manifestations such as the pattern of arthritis. However, characteristics of SpA associated with FMF such as clinical characteristics and treatment outcomes have been poorly documented and additional data is required on this topic.Objectives:To study the clinical and treatment characteristics of patients associated with FMF and SpA.Methods:Twenty-eight patients with FMF and SpA who were registered in our database were included in the study. Demographic, clinical, and laboratory data were collected. HLA-B27, MEFV gene mutations were recorded. Pelvic radiographs and sacroiliac joint magnetic resonance imaging (MRI) (if present) were scored based on the modified New York criteria (mNYc) and ASAS MRI definitions respectively. Treatment data were also recorded.Results:There were 28 FMF-SpA patients in the study (mean age 45.1±16.4 years, 57.2% male). The mean age of onset of FMF and SpA were 31.9±17.9 and 35.5±16.2 years respectively. SpA patients were predominantly axial (n=21, 75%), and only 7 (25%) were mainly peripheral type. Fifteen (53.5%) patients were satisfying mNYc for AS. Four (14%) patients were fulfilling ASAS non radiographic axial SpA definition. Bone marrow edema was detected in (36%) of the patients who underwent MRI (n=14). Two (7.1%) patients had SpA symptoms but did not classify into any of the ASAS arms. Arthritis observed in 19 (67.8%) patients with mostly in oligoarthritis type (79%). Ankle and knees were the most affected joints. Total hip replacement was present in 7% of the patients. Amyloidosis confirmed by biopsy was detected in 4 (14%) patients. Enthesitis (11%), uveitis (11%), Chron’s disease (7%), dactylitis (3%), and psoriasis (3%) was also noted. Nearly %30 patients required non IL-1 biologic therapy (BTx) to control SpA symptoms (axial 70%, peripheral 30%). 40% of the patients needed to switch non IL-1 BTx to another biologic agent because of lack of efficacy on SpA symptoms (25%) or due to the adverse event (25%) and active FMF not responding to non IL-1 biological agent (50%).Conclusion:We showed the following: 1) more female predominance in FMF-SpA patients compared to classic SpA, 2) FMF-SpA patients had lower frequency of HLA B27, 3) up to %30 of the patients required non-IL-1 BTx to control SpA symptoms and 4) in patients on non IL-1 BTx FMF symptoms responded in 80%.Table 1.The clinical characteristics of FMF-SPA patientsAge*45.1±16.4Male, n (%)16 (57.2)SpA symptom duration,years*9.5±7.0FMF symptom duration,years*12.6±9.6HLA-B27 positivity, n (%)5 (29.4)Mainly axial involvement, n (%)21 (75)Mainly peripheral involvement, n (%)7(25)mNY positivity, n (%)15 (53.5)MEFV (M694V) mutation18MEFV (non M694V) mutation19Amyloidosis, n (%)4 (14.2)Non IL-1 biological treatment for SpA symptoms, n (%)10 (35.7)*(mean ±S.D)Disclosure of Interests:None declared

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POS1368 ANTI-IL-1 THERAPIES IN COLCHICINE-RESISTANT OR İNTOLERANT PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER: SINGLE CENTER EXPERIENCE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3257 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 966.1-966

Author(s):

M. E. Derin ◽

B. Karakaş ◽

B. Karataş ◽

N. Çabuk Çelik ◽

İ. Yalçin ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Interleukin 1 ◽

Mefv Gene ◽

Gene Mutations ◽

Recurrent Fever ◽

Long Term Effects ◽

Single Center Experience ◽

Eular Recommendations ◽

Mediterranean Fever

Background:Familial Mediterranean Fever (FMF) is a hereditary auto-inflammatory disease characterized by recurrent fever and serosal inflammation (1). The goal of FMF treatment is to prevent the attacks and to minimize subclinical inflammation between attacks The main treatment of FMF is colchicine however anti-interleukin-1 treatments are recommended in colchicine resistant and/or intolerant FMF patients (2).Objectives:The aim of this study is to evaluate the efficacy of anti-interleukin-1 (anti-IL-1) agents in 81 FMF patients with resistant/intolareted to colchicine or complicated with amyloidosis.Methods:Between January 2014 and December 2020, eighty-one patients who were diagnosed as FMF according to the criteria of Tel-Hashomer that following-up at Cumhuriyet University Medical Faculty Rheumatology-Internal Medicine Department were included in to the study.Results:45 (55.6%) male and 36 (44.4%) female were included in the study. The median age of the patients was 25 years (min:17-max: 60) and the median age at diagnosis was 15 years (min 3-max 46). 44 patients (54.3%) used Anakinra (100 mg/day), and 27 (45.7%) canakinumab (150mg/8month) were used. 49 cases were resistant to colchicine,16 were intolerant to colchicine, 16 (20%) cases were comlicated with amyloidosis. 10 patients had renal transplantation. MEFV gene mutations are shown in Table 1. Median duration of anti-IL-1 agent use was 24 month (min:4-max 52). 9 patients were resistant to anakinra, 18 patients had side effects which anakinra related. After a median follow up 12 months overall clinical response was %95 (frequency of attacks <1/6months). median proteinuria decreased from 3500 mg /day to median 1500 mg /day (p: 0.04) (Table 2). IL-6 treatment was started in 4 patients because of ineffective canakinumab. Five pregnant patients were followed up with anakinra during pregnancy and there were no problems.Conclusion:Anti-interleukin-1 agents are effectively and safely in the treatment of FMF patients. There are still unanswered questions in FMF treatment such as other factors affecting the frequency of attacks, colchicine resistance is not defined precisely and the importance of some mutations. The effect of anti IL-1 agents on FMF patients with amyloidosis is not clearly. According to our experience, these treatments are effective in patients with glomerular filtration rate> 60 ml/min. For answers to these and similar questions, Large and long follow-up studies are needed for long-term effects.References:[1]Özen S, Batu ED, Demir S., Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management. Front Immunol. 2017 Mar 23;8:253. doi: 10.3389/fimmu.2017.00253. eCollection 2017.[2]Seza Özen ve ark. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis. 2016 Apr;75(4):644-51.Disclosure of Interests:None declared

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POS1302 THE MUSCULOSKELETAL SYSTEM MANIFESTATIONS IN CHILDREN WITH FAMILIAL MEDITERRANEAN FEVER

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1169 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 933.1-933

Author(s):

F. Demir ◽

S. Canbek ◽

B. Sözeri

Keyword(s):

Familial Mediterranean Fever ◽

Periodic Fever ◽

Mefv Gene ◽

Clinical Manifestations ◽

Musculoskeletal Symptoms ◽

Compound Heterozygous ◽

M694v Mutation ◽

Musculoskeletal Manifestations ◽

Mediterranean Fever ◽

Calf Pain

Background:Familial Mediterranean fever (FMF) is a monogenic inherited periodic fever syndrome presenting with episodes of self-limiting fever and inflammation of serosal membranes. The attacks emerge with arthritis were defined as one of the major diagnostic criteria besides involvement of serosal membranes. Non-specific musculoskeletal findings such as myalgia, arthralgia, transient synovitis, and more rare manifestations like protracted febrile myalgia can also be seen in FMF patients attacksObjectives:We aim to reveal the frequency and genotype association of musculoskeletal manifestations in children with FMF.Methods:The patients diagnosed with FMF between January 1, 2017 and June 1, 2019, and followed for at least 6 months in our pediatric rheumatology clinic were included in the study. Musculoskeletal manifestations of patients were enrolled. The patients were grouped according to the “Mediterranean Fever” (MEFV) gene variants. Musculoskeletal manifestations of the patients were compared between the groupsResults:The study group included 634 children with FMF (336 female and 298 male, F/M: 1.13/1). The clinical manifestations of patients in attack period were as follows: 99% of the patients had fever, 87.3% had abdominal pain, 20.7% had chest pain, 11.3% had vomiting, 10.7% had erysipelas like erythema, and 9.3% had headache. The musculoskeletal symptoms were accompanied by 58.6% (n: 372) of the patients during the attack period. The most common musculoskeletal manifestation was found as arthralgia (32.6%, n: 206). Also, the other musculosceletal manifestations were found as follows during attacks; arthritis in 23.7% (n: 150), myalgia in 20.5% (n: 130), exertional calf pain in 6.5% (n: 41), and protracted febrile myalgia in 1% (n: 7) of the patients. It was observed that the musculoskeletal manifestations were significantly higher in patients with homozygous M694V variant in exon-10 (p=0.017). Also, it was found that the musculoskeletal manifestations are more common in the attack periods of patients carrying the M694V variant in at least one allele (p = 0.019).Conclusion:It was determined that the musculoskeletal manifestations were seen as an attack symptom in more than half of FMF patients. Also, homozygous and compound heterozygous MEFV mutations including M694V variant found as a risk factor for emerge of musculoskeletal manifestations. In children with unexplained and recurrent musculoskeletal symptoms, especially in ethnicities with the high frequency of FMF, analysis of MEFV gene can help reveal the underlying cause.References:[1]Brik R, Shinawi M, Kasinetz L, Gershoni-Baruch R. The musculoskeletal manifestations of familial Mediterranean fever in children genetically diagnosed with the disease. Arthritis Rheum 2001;44:1416-9.[2]Jarjour RA, Dodaki R. Arthritis patterns in familial Mediterranean fever patients and association with M694V mutation. Mol Biol Rep 2011;38:2033-6.Disclosure of Interests:None declared

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Analysis of mutations of the MEFV gene in women with infertility and familial Mediterranean fever

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2021.02.27-38 ◽

2021 ◽

pp. 27-38

Author(s):

П.О. Соцкий ◽

О.Л. Соцкая ◽

Т.Ф. Саркисян ◽

А.С. Айрапетян ◽

А.Р. Егиазарян ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Mefv Gene ◽

Delayed Diagnosis ◽

Reproductive Age ◽

Clear Correlation ◽

Renal Amyloidosis ◽

Reproductive Disorders ◽

M694v Mutation ◽

Mediterranean Fever ◽

Fertile Women

Изучение взаимосвязи между мутациями в гене MEFV и бесплодием создает предпосылки для оптимизации диагностики и профилактики репродуктивных нарушений у женщин с семейной средиземноморской лихорадкой (ССЛ). Цель: поиск корреляций между мутациями в гене MEFV и бесплодием в большой когорте армянских пациенток. В период с 1998 по 2018 годы в Центре медицинской генетики и первичной охраны здоровья были обследованы 32 000 человек на наличие мутаций в гене MEFV. Из этой группы выбраны женщины (4577) репродуктивного возраста (18-49 лет), у которых был установлен клинический диагноз ССЛ на основании критериев Тel-Hashomer, подтвержденный генетическим тестированием. Комплексное обследование репродуктивной функции произведено у 373 женщин: 211 пациенток с ССЛ и у 162 женщин с репродуктивными расстройствами без ССЛ. Обнаружено, что гомозиготный генотип M694V/M694V, выявленный у 11,5% женщин с ССЛ, ассоциируется с тяжелым клиническим течением и развитием амилоидоза у 1,5% (р=0,028). Бесплодие чаще встречается у гомозиготных по M694V (90,9%) и M680I (100%) пациенток (р<0,009). Наиболее распространенная у армянских женщин репродуктивного возраста мутация M694V (40,7%) при бесплодии встречается чаще (69,7%), чем у фертильных женщин (30,3%) (p<0,009). Выявлена ассоциация между нерегулярным применением колхицина или использованием низкой дозы препарата и бесплодием у пациенток с ССЛ (88,4%) (р<0,001). Отсроченная диагностика свыше 10 лет наблюдалась у 80,7% бесплодных пациенток с ССЛ по сравнению с 19,3% у фертильных женщин (р<0,007). Таким образом, бесплодие в значительной степени связано с гомозиготными генотипами по мутациям M694V или M680I, которые ассоциируются с более тяжелым течением заболевания. Пациентки с ССЛ имеют сопоставимые репродуктивные показатели с женщинами без ССЛ. Бесплодие формируется под влиянием таких модифицирующих факторов, как социальный статус, нерегулярный прием колхицина, задержка диагностики свыше 10 лет. The study of the relationship between mutations in the MEFV (MEditerranean FeVer) gene and infertility creates opportunity for optimizing the diagnosis and prevention of reproductive disorders in women with familial Mediterranean fever (FMF). Data were collected from the patients registered in 1998- 2018 at the Center for Medical Genetics and Primary Health Care. From the cohort of 32000 patients analyzed for mutations in the MEFV gene, only women (4577) of reproductive age (18-49 years old) were selected, with clinical diagnosis FMF according to the International Tel-Hashomer criteria and confirmed by genetic testing. Comprehensive monitoring of reproductive function was performed in 373 women - 211 FMF patients and 162 non FMF women with reproductive disorders. Homozygous genotype M694V/M694V (11.5%) is associated with severe disease and renal amyloidosis (1.5%) (p=0.028). Infertility was revealed in 90.9% patients homozygous for M694V and 100% for M680I mutations (p<0.009). M694V mutation in population of women of reproductive age was more common in FMF patients with infertility (68.8%) compare to fertile women (31.2%) (p<0.009). A clear correlation between irregular uptakes or a low dose of colchicine and infertility among investigated FMF patients (88.4%) (p <0.001) was revealed. A delayed diagnosis of over 10 years was observed in 80.7% of infertile patients with FMF compared with 19.3% in fertile women (p<0.007). Infertility is largely associated with homozygous M694V or M680I genotypes of MEFV gene. Patients with FMF have a comparable prior-reproductive system with healthy controls. Infertility is formed under the influence of modifying factors such as social status, irregular intake of colchicine, and delayed diagnosis for more than 10 years.

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