The Phenotype-Genotype Correlations of FMF Patients: A Single Center Study
DOI:
https://doi.org/10.47672/ajhmn.2335Keywords:
Diagnosis, Familial Mediterranean Fever, Genetic, MEFV, TreatmentAbstract
Purpose: Familial Mediterranean Fever (FMF) is an autosomal recessive, auto-inflammatory disease that is characterized by recurrent fever and polyserositis episodes like peritonitis, arthritis, and pleuritis. The disease occurs most commonly in populations of Jewish, Turkish, Armenian, and Arabian origin. We aimed to show the genotype-phenotype relationship in FMF patients in our centre.
Materials and Methods: We conducted a retrospective analysis of the medical registries of 200 FMF pediatric patients from Sisli Hamidiye Etfal Education and Research Hospital, Department of Pediatrics, Pediatric Nephrology Policlinic between 2011 and 2017. The diagnosis was based on the Tel-Hashomer clinical diagnostic criteria. We used the severity score recommended by Pras in 1998. Clinical data and baseline investigations were collected. Mutation analysis was performed by the amplification-refractory mutation system (ARMS)-PCR method.
Findings: Females represented 54% and ages ranged from 40-210 months. The most frequent symptoms were abdominal pain, fever, and arthralgia.Among the 200 patients, 41 (20,5%) were homozygous, 63 (31,5%) were compound heterozygous, and 96 (48%) were heterozygous for MEFV mutations. The first 3 most common mutations were heterozygotus R202Q, M694V/R202Q and heterozygotus E148Q respectively., which was statistically significant. M694V mutation was positive in at least one allele in 72 patients studied. The symptom of fever and arthralgia were found to be significantly higher in patients with M694V mutation. Also, the number of episodes in one year before treatment, PRAS score and the values of fibrinogen during episodes were higher in M694V patients as a result, the age at diagnosis was found to be earlier in patients with homozygotus M694V mutation. The ratio of female gender and myalgia was significantly higher in patinets with the mutation of R202Q homozygotus. The number of episodes in one year before treatment was lower in R202Q patients when compared to the M694V carriers, therefore the initiation age to colchicine was later in the R202Q group which was statistically significant.
İmplications to Theory, Practice and Policy: Our results support the notion that the genotype influences the phenotype as regards clinical manifestations, disease severity, and colchicine response.
Downloads
References
Lidar M, Livneh A.Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med. 2007; 65: 318-324.
Tekin M, Yalcınkaya F,Tümer N et al. Clinical, laboratory and molecular characteristics of children with familiall Mediterranean fever-associated vasculitis. Acta Pediatr 2000;89:177-82.
Majeed HA, Rawashdeh M, el-Shanti H, Qubain H, Khuri-Bulos N, Shahin HM. Familial Mediterranean fever in children: the expanded clinical profile. QJM. 1999; 92: 309-318.
Baskin E, Saatci U. Familial Mediterranean Fever. Curr Rheumatol Rev. 2006; 2: 101-108.
Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, Tutar E,Ozen S, Topaloglu R, Yılmaz E, Arici M, Bakkaloglu A, Besbas N, Akpolat T, Dinc A, Erken E; Turkish FMF Study Group. Familial Mediterranean fever (FMF) in Turkey: Results of a nationwide multicenter study. Medicine (Baltimore). 2005; 84: 1-11.
Kasapcopur O, Arısoy N. Ailesel Akdeniz Ateşi ve diğer otoenflamatuar hastalıklar.Turk Pediatri Arşivi 2006;41:9-17.
Pras, M."Familial Mediterranean fever: from the clinical syndrome to the cloning of the pyrin gene." Scand J Rheumatol, 27(2); 92-7,1998
Ergüven M ÜR, Cebeci A N, Pelit M. Ailevî Akdeniz ateşinin demografik, klinik ve genetik özellikleri ile tedaviye yanıtı: 120 vakalık tek merkez deneyimi. Çocuk Sağlığı ve Hastalıkları Dergisi 2006; 49: 283-290
Türkiye nüfüs ve sağlık araştırması 2008, http://www.hips.hacettepe.edu.tr/tnsa2008/.
Kone Paut I, Dubuc M, Sportouch J, Minodier P, Garnier JM, Touitou I. Phenotype-genotype correlation in 91 patients with familial Mediterranean fever reveals a high frequency of cutaneomucous features. Rheumatology. 2000; 39: 1275-1279.
Kilic et al. Relationship between clinical findigs and genetic mutations in patients with Familia Mediterranean Fever.Pedatric Rheumatology(2015)13:59.
Çankaya et al. Clinical Significance of R202Q Alteration of MEFV Gene in Children With Familial Mediterranean Fever. Arch Rheumatol 2015;30(x):i-vi.
Başarslan F,Yengil E,Göğebakan B. Evaluation of the Patients With the Diagnosis of Familial Mediterranean Fever in Clinical and Genetic Aspects: Smyrna Tıp Dergisi 2012.
Akar N, Misiroglu M, Yalcinkaya F, Akar E, Cakar N, Tümer N, Akcakus M, Tastan H, Matzner Y. MEFV mutations in Turkish patients suffering from Familial Mediterranean Fever. Hum Mutat. 2000; 15: 118-119.
Ozen S, Demirkaya E, Amaryan G, Koné-Paut I, Polat A, Woo P, Uziel Y, Modesto C, Finetti M, Quartier P, Papadopoulou-Alataki E, Al-Mayouf SM, Fabio G, Gallizzi R, Cantarini L, Frenkel J, Nielsen S, Hofer M, Insalaco A, Acikel C, Ozdogan H, Martini A, Ruperto N, Gattorno M; Paediatric Rheumatology International Trials Organisation; Eurofever Project. Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children. Ann Rheum Dis. 2014; 73: 662-667.
Mansfield E, Chae JJ, Komarow HD, et al. The familial Mediterranean fever protein, pyrin, associates with microtubules and colocalizes with actin filaments. Blood 2001; 98:851-859.
Topaloğlu R, Özaltın F, Yılmaz E. E148Q is adisease causing MEFV mutation: a phenotypic evaluation in patients with familial Mediterranean fever. Ann Rheumatic Dis 2005; 64:750-752
Jarjour RA, Al-Berrawi S. Familial Mediterranean fever in Syrian children: phenotype-genotype correlation. Rheumatol Int. 2015; 35: 629-634.
Berdeli A, Cura A, Mir S, Serdaroglu E, Ozkayin N. MEFV gene mutations in children with familial mediterranean fever. BANTAO Journal. 2003; 1: 13.
Medlej-Hashim M, Delague V, Choueri E, et al. Amyloidosis in Familial Mediterranean Fever patients: correlation with MEFV genotype and SAAI and MICA polymorphisims effects. BMC Med Genet 2004;5(4):1-6.
Ebrahimi-Fakhari D et al.Familial Mediterranean fever in Germany:clinical presentation and amyloidosis risk.Scand J rheumatol 2013;42:52-58.
Brik R Shinawi M, Kepten I, Berant M, Gershoni-Baruch R. Familial Mediterranean fever: Clinical ant genetic characterization in a mixed pediatric population of Jewish and Arab patients. Pediatrics. 1999; 103: 70.
Giaglis, S., V. Papadopoulos, et al. (2007). "MEFV alterations and population genetics analysis in a large cohort of Greek patients with familial Mediterranean fever." Clin Genet 71(5): 458-67.
Karakus N, Yigit S, Inanir A, Inanir S, Toprak H, Okan S. ‘’Association between sequence variations of the Mediterranean fever gene and fibromyalgiasyndrome in a cohort of Turkish patients.’’ Clin Chim Acta. 2012 Dec 24;414:36-40.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Dr. Gozde Gurpinar, Dr. Nurver Akinci, Dr. Gul Ozcelik, Dr. Zeynep Yildiz Yildirmak
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution (CC-BY) 4.0 License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
