Year 2015,
Volume: 42 Issue: 1, 61 - 65, 09.05.2015
Abstract
Objective: This retrospective study aimed to evaluate the clinical symptoms and the MEFV mutation ratios of the 186 patients diagnosed as Familial Mediterranean Fever.Methods: Age, sex, admission symptoms, family history, and the MEFV mutation test cases of the 186 patients followed as Familial Mediterranean Fever were evaluated retrospectively. MEFV gene was analyzed with DNA sequence analysis after amplifying the exons 1.-10. using PCR method. Results: There were 84 male and 102 female in the study, and the mean age was 9.45 ± 4.40 years. 26.9% of the patients had close relationship between the parents, and 25.8% had a family history of AAA. The most common symptoms were abdominal pain (92.5%), fever (89.2%), and arthralgia (24.2%) respectively. The most common mutations were R202Q (33.3%), M694V (22.6%), E148Q (22%), V726A (7.5%), R761H (4.3%), M680I (3.8%), and the others (6.5%) respectively. 21.5% homozygous, 67.7% heterozygous, and 10.8% compound heterozygous mutations of AAA were detected. Conclusion: FMF is a common disease in our country and has difficulties in the differential diagnosis. In recent years molecular genetically methods are considered more commonly for the diagnosis. The results of this study showed that our AAA patients have a wide range of mutations, and supported the heterogeneity of MEFV gene mutations in AAA
References
- Çobankara V, Kiraz S. Ailesel Akdeniz Ateşi. Hacettepe Tıp
- Dergisi 2000;31:310-319.
- Barakat MH, Karnik AM, Majeed HW, et al. Familial Mediterranean
- fever (recurrent hereditary polyserositis) in Arabs
- study of 175 patients and review of the literature. Q J Med
- ;60:837-847.
- Çakmak E, Ece A, Kelekçi S, ve ark. Ailesel Akdeniz ateşli
- çocuklarda atak sırasındaki ve ataksız dönemdeki akut faz
- yanıtlarının karşılaştırılması. J Clin Exp Invest 2013;4:213-
- -
- Direskeneli H, Ozdogan H, Korkmaz C, et al. Serum soluble
- intercellular adhesion molecule 1 and interleukin 8 levels in
- Familial Mediterranean Fever. J Rheumatol 1999;26:983-
- -
- The international FMF Consortium: Ancient missense mutations
- in a new member of the RoRet gene family are likely
- to cause FMF. Cell 1997; 90: 797-807.
- The French FMF Consorsium. Candidate gene for familial
- Mediteranean fever. Natur Genet 1997;17:25-31.
- Drenth JPH, Van Der Meer JW. Hereditary periodic fever. N
- Engl J Med 2003;345:1748-1757.
- Kastner DL. The genetic of inflammation. Hosp Prac
- ;33:131-146.
- Mor A, Gal R, Livneh A. Abdominal and digestive system
- associations of familial Mediterranean fever. Am J Gastroenterol
- ;98:2594-604.
- Touitou I, Lesage S, McDermott M. et al. Infevers: an
- evolving mutation database for auto-inflammatory syndromes.
- Hum Mutat. 2004;24:194-198.
- Saatçi Ü, Bakkaloğlu A, Özen S, Beşbaş N. Familial
- Mediterranean and amyloidosis in children. Acta Paediatr
- ;82:705-706.
- Bakkaloglu A. Familial Mediterranean fever. Pediatr
- Nephrol 2003;18:853-859.
- Mansour I, Delague V, Cazeneuve C, et al. Familial Mediterranean
- fever in Lebanon: mutation spectrum, evidence
- for cases in Maronites, Greek orthodoxes, Greek catholics,
- Syriacs and Chiites and for an association between amyloidosis
- and M694V and M694I mutations. Eur J Hum Genet
- ;9:51-55.
- Daniels M, Shohat T, Brenner-Ullman A, Shohat M. Familial
- Mediterranean fever: High gene frequency among
- the non-Ashkenazic and Ashkenazic Jewish populations in
- Israel. Am J Med Genet 1995;55:311-314.
- Dundar M, Emirogullari EF, Kiraz A, et al. Common Familial
- Mediterranean Fever gene mutations in a Turkish
- cohort. Mol Biol Rep 2011;38:5065-5069.
- Goldfinger S.E. Colchicine for Familial Mediterranean fever.
- (Letter) New Eng J Med 1972; 287:1302.
- Tunca M, Akar S, Onen F, et al. Turkish FMF Study Group.
- Familial Mediterranean fever (FMF) in Turkey: results
- of a nationwide multicenter study. Medicine (Baltimore)
- ;84:1-11.
- Gershoni Baruch R. Familial Familial Mediterranean fever:
- Clinical and genetic characterization in a mixed pediatric
- population of Jewish and Arab patients. Pediatrics
- ;103: e70.
- Majeed HA, Rawashdeh M, el-Shanti H, et al. Familial
- Mediterranean fever in children: The expanded clinical
- profile. QJM 1999;92:309-318.
- Gedalia A, Adar A, Gorodischer R. Familial Mediterranean
- fever in children. J Rheumatol Suppl 1992;35:1-9.
- Turkish FMF Study Group. Familial Mediterranean fever in
- Turkey; Results of a nationwide multicenter study. Medicine
- ;84:1-11.
- Mimouni A, Magal N, Stoffman N, et al. Familial Mediterranean
- fever: effects of genotype and ethnicity on inflammatory
- attacks and amyloidosis. Pediatrics 2000;105:E70.
- Solak M, Yıldız H, Köken R, et al. Ailevi Akdeniz atesi
- ön tanisi alan 165 olgunun MEFV geni mutasyonlarinin incelenmesi.
- Turkiye Klinikleri J Med Sci 2008;28:117-122.
- Ergüven M, Üçel R, Cebeci AN, 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.
- Ozen S, Demirkaya E, Amaryan G, et al. 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-
- -
- Örün E, Yalçınkaya F. Türk tıbbında ailevi Akdeniz ateşi
- hastalığı ve amiloidoz. Nefroloji Diyaliz ve Transplantasyon
- Dergisi 2003;12:1-7.
- Çiler Erbağ Ç, Akın Y, Ağızkuru T, ve ark. Ailesel Akdeniz
- Ateş tanılı olgularımız. Kartal Eğitim ve Araştırma Hastanesi
- Tıp Dergisi 2008;19:131-137.
- Koné Paut I, Dubuc M, Sportouch J, at al. Phenotype-genotype
- correlation in 91 patients with familial Mediterranean
- fever reveals a high frequency of cutaneomucous features.
- Rheumatology (Oxford) 2000;39:1275-1279.
- Rawashdeh MO, Majeed HA. Familial Mediterranean fever
- in Arab children: the high prevalence and gene frequency.
- Eur J Pediatr 1996;155:540-544.
- Nir-Paz R, Ben-Chetrit E, Pikarsky E, ve ark. Unusual presentation
- of familial Mediterranean fever: role of genetic
- diagnosis. Ann Rheum Dis 2000;59:836-838.
- Giancanehttp://ard.bmj.com/content/early/2015/01/27/
- annrheumdis-2014-206844.full - aff-1 G, Haar NT,Wulffraathttp://ard.bmj.com/content/early/2015/01/27/annrheumdis-2014-206844.full- aff-1 N. et al. Evidencebased recommendations for genetic diagnosis of familial Mediterranean fever. Ann Rheum Dis 2015;10:1-7.
- Yalçınkaya E, Güran Ş, Nas B, ve ark. Ailesel Akdeniz ateşi
- ön tanısı alan olgularda MEFV gen analiz sonuçlarının önemi.
- Erciyes Tıp Dergisi 2006;1:19-24.
- Evliyaoğlu O, Bilici S, Yolbaş İ, ve ark. Diyarbakır yöresi
- ailevi Akdeniz ateşli çocuklarda MEFV gen mutasyon sıklıkları.
- Dicle Tıp Dergisi 2009;36:80-84.
- Medlej-Hashim M, Delague V, Choueri E, et al. Amyloidosis
- in Familial Mediterranean Fever patients: correlation
- with MEFV genotype and SAAI and MICA polymorphisms
- effects. BMC Med Genet 2004;5:1-6.
- Padeh S, Shinar Y, Pras E, et al. Clinical and diagnostic
- value of genetic testing in 216 Israeli children with familial
- Mediterranean fever. J Rheumatol 2003;30:185-190.
- Shohat M, Magal N, Shohat T, et al. Phenotype-genotype
- correlationin FMF: evidence for an association between
- Met694Val and amyloidosis. Eur J Hum Genet 1999;7:287-
- -
- Cazeneuve C, Sarkisian T, Pecheux C, et al. MEFV-gene
- analysis in Armenian patients with familial Mediterranean
- fever: diagnostic value and unfavorable renal prognosis of
- the M694V homozygous genotype-genetic and therapeutic
- implications. Am J Hum Genet 1999;65:88-97.
Ailevi Akdeniz ateşi tanısı alan 186 olgunun klinik semptom ve MEFV geni mutasyonlarının incelenmesi
Abstract
Amaç: Bu çalışmada Ailevi Akdeniz Ateşi (AAA) tanı- sı alan ve MEFV mutasyon testi yapılan 186 hastanın retrospektif olarak semptom ve mutasyon oranı tespiti amaçlanmıştır. Yöntemler: Ailesel Akdeniz Ateşi tanısıyla izlenen 186 hastanın yaşı, cinsiyeti, geliş yakınmaları, aile öyküleri ve MEFV mutasyon testi durumlarını geriye dönük olarak değerlendirmeye alındı. MEFV geni 1. - 10. ekzonlar PCR yöntemi ile amplifiye edildikten sonra DNA dizi analizi ile çalışıldı. Bulgular: Hastaların 84’ü erkek, 102’si kız olup yaş ortalaması 9,45 ± 4,40 (yaş aralığı: 2-17) yıl idi. Olguların % 26,9’ unun anne baba arasında yakın akrabalık ve % 25,8’inin ailelerinde AAA öyküsü vardı. Sıklık sırasına göre başvuru nedenleri karın ağrısı, (%92,5), ateş (%89,2) ve eklem ağrıları (%24,2) yer aldı. Tespit edilen mutasyonlar sıklık sırasına göre R202Q (% 33,3), M694V (%22,6), E148Q (% 22), V726A (%7,5), R761H (%4,3), M680I (%3,8) ve diğerleri (%6,5) genotipi mutasyonlar olarak belirlendi. Hastaların % 21,5 homozigot ve %67,7’si heterozigot ve %10,8’inde birleşik heterozigot AAA mutasyonu saptandı. Sonuç: AAA, Ülkemizde sık görülen ve ayrıcı tanıda güç- lük yaşanan bir hastalıktır. Son yıllarda AAA tanısında moleküler genetik yöntemler önem kazanmıştır. Bu çalışmanın sonuçları AAA’lı hastalarda MEFV gen mutasyonundaki heterojeniteyi desteklemiş ve hastalarımızın geniş bir mutasyon yelpazesine sahip olduğunu göstermiştir. Anahtar kelimeler: Ailesel Akdeniz ateşi, MEFV gen mutasyon, semptom
References
- Çobankara V, Kiraz S. Ailesel Akdeniz Ateşi. Hacettepe Tıp
- Dergisi 2000;31:310-319.
- Barakat MH, Karnik AM, Majeed HW, et al. Familial Mediterranean
- fever (recurrent hereditary polyserositis) in Arabs
- study of 175 patients and review of the literature. Q J Med
- ;60:837-847.
- Çakmak E, Ece A, Kelekçi S, ve ark. Ailesel Akdeniz ateşli
- çocuklarda atak sırasındaki ve ataksız dönemdeki akut faz
- yanıtlarının karşılaştırılması. J Clin Exp Invest 2013;4:213-
- -
- Direskeneli H, Ozdogan H, Korkmaz C, et al. Serum soluble
- intercellular adhesion molecule 1 and interleukin 8 levels in
- Familial Mediterranean Fever. J Rheumatol 1999;26:983-
- -
- The international FMF Consortium: Ancient missense mutations
- in a new member of the RoRet gene family are likely
- to cause FMF. Cell 1997; 90: 797-807.
- The French FMF Consorsium. Candidate gene for familial
- Mediteranean fever. Natur Genet 1997;17:25-31.
- Drenth JPH, Van Der Meer JW. Hereditary periodic fever. N
- Engl J Med 2003;345:1748-1757.
- Kastner DL. The genetic of inflammation. Hosp Prac
- ;33:131-146.
- Mor A, Gal R, Livneh A. Abdominal and digestive system
- associations of familial Mediterranean fever. Am J Gastroenterol
- ;98:2594-604.
- Touitou I, Lesage S, McDermott M. et al. Infevers: an
- evolving mutation database for auto-inflammatory syndromes.
- Hum Mutat. 2004;24:194-198.
- Saatçi Ü, Bakkaloğlu A, Özen S, Beşbaş N. Familial
- Mediterranean and amyloidosis in children. Acta Paediatr
- ;82:705-706.
- Bakkaloglu A. Familial Mediterranean fever. Pediatr
- Nephrol 2003;18:853-859.
- Mansour I, Delague V, Cazeneuve C, et al. Familial Mediterranean
- fever in Lebanon: mutation spectrum, evidence
- for cases in Maronites, Greek orthodoxes, Greek catholics,
- Syriacs and Chiites and for an association between amyloidosis
- and M694V and M694I mutations. Eur J Hum Genet
- ;9:51-55.
- Daniels M, Shohat T, Brenner-Ullman A, Shohat M. Familial
- Mediterranean fever: High gene frequency among
- the non-Ashkenazic and Ashkenazic Jewish populations in
- Israel. Am J Med Genet 1995;55:311-314.
- Dundar M, Emirogullari EF, Kiraz A, et al. Common Familial
- Mediterranean Fever gene mutations in a Turkish
- cohort. Mol Biol Rep 2011;38:5065-5069.
- Goldfinger S.E. Colchicine for Familial Mediterranean fever.
- (Letter) New Eng J Med 1972; 287:1302.
- Tunca M, Akar S, Onen F, et al. Turkish FMF Study Group.
- Familial Mediterranean fever (FMF) in Turkey: results
- of a nationwide multicenter study. Medicine (Baltimore)
- ;84:1-11.
- Gershoni Baruch R. Familial Familial Mediterranean fever:
- Clinical and genetic characterization in a mixed pediatric
- population of Jewish and Arab patients. Pediatrics
- ;103: e70.
- Majeed HA, Rawashdeh M, el-Shanti H, et al. Familial
- Mediterranean fever in children: The expanded clinical
- profile. QJM 1999;92:309-318.
- Gedalia A, Adar A, Gorodischer R. Familial Mediterranean
- fever in children. J Rheumatol Suppl 1992;35:1-9.
- Turkish FMF Study Group. Familial Mediterranean fever in
- Turkey; Results of a nationwide multicenter study. Medicine
- ;84:1-11.
- Mimouni A, Magal N, Stoffman N, et al. Familial Mediterranean
- fever: effects of genotype and ethnicity on inflammatory
- attacks and amyloidosis. Pediatrics 2000;105:E70.
- Solak M, Yıldız H, Köken R, et al. Ailevi Akdeniz atesi
- ön tanisi alan 165 olgunun MEFV geni mutasyonlarinin incelenmesi.
- Turkiye Klinikleri J Med Sci 2008;28:117-122.
- Ergüven M, Üçel R, Cebeci AN, 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.
- Ozen S, Demirkaya E, Amaryan G, et al. 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-
- -
- Örün E, Yalçınkaya F. Türk tıbbında ailevi Akdeniz ateşi
- hastalığı ve amiloidoz. Nefroloji Diyaliz ve Transplantasyon
- Dergisi 2003;12:1-7.
- Çiler Erbağ Ç, Akın Y, Ağızkuru T, ve ark. Ailesel Akdeniz
- Ateş tanılı olgularımız. Kartal Eğitim ve Araştırma Hastanesi
- Tıp Dergisi 2008;19:131-137.
- Koné Paut I, Dubuc M, Sportouch J, at al. Phenotype-genotype
- correlation in 91 patients with familial Mediterranean
- fever reveals a high frequency of cutaneomucous features.
- Rheumatology (Oxford) 2000;39:1275-1279.
- Rawashdeh MO, Majeed HA. Familial Mediterranean fever
- in Arab children: the high prevalence and gene frequency.
- Eur J Pediatr 1996;155:540-544.
- Nir-Paz R, Ben-Chetrit E, Pikarsky E, ve ark. Unusual presentation
- of familial Mediterranean fever: role of genetic
- diagnosis. Ann Rheum Dis 2000;59:836-838.
- Giancanehttp://ard.bmj.com/content/early/2015/01/27/
- annrheumdis-2014-206844.full - aff-1 G, Haar NT,Wulffraathttp://ard.bmj.com/content/early/2015/01/27/annrheumdis-2014-206844.full- aff-1 N. et al. Evidencebased recommendations for genetic diagnosis of familial Mediterranean fever. Ann Rheum Dis 2015;10:1-7.
- Yalçınkaya E, Güran Ş, Nas B, ve ark. Ailesel Akdeniz ateşi
- ön tanısı alan olgularda MEFV gen analiz sonuçlarının önemi.
- Erciyes Tıp Dergisi 2006;1:19-24.
- Evliyaoğlu O, Bilici S, Yolbaş İ, ve ark. Diyarbakır yöresi
- ailevi Akdeniz ateşli çocuklarda MEFV gen mutasyon sıklıkları.
- Dicle Tıp Dergisi 2009;36:80-84.
- Medlej-Hashim M, Delague V, Choueri E, et al. Amyloidosis
- in Familial Mediterranean Fever patients: correlation
- with MEFV genotype and SAAI and MICA polymorphisms
- effects. BMC Med Genet 2004;5:1-6.
- Padeh S, Shinar Y, Pras E, et al. Clinical and diagnostic
- value of genetic testing in 216 Israeli children with familial
- Mediterranean fever. J Rheumatol 2003;30:185-190.
- Shohat M, Magal N, Shohat T, et al. Phenotype-genotype
- correlationin FMF: evidence for an association between
- Met694Val and amyloidosis. Eur J Hum Genet 1999;7:287-
- -
- Cazeneuve C, Sarkisian T, Pecheux C, et al. MEFV-gene
- analysis in Armenian patients with familial Mediterranean
- fever: diagnostic value and unfavorable renal prognosis of
- the M694V homozygous genotype-genetic and therapeutic
- implications. Am J Hum Genet 1999;65:88-97.
There are 120 citations in total.
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Research Articles |
| Authors | |
| Publication Date | May 9, 2015 |
| Submission Date | May 9, 2015 |
| Published in Issue | Year 2015 Volume: 42 Issue: 1 |