Cekin Nilgun, Akyurek Murat Eser, Pinarbasi Ergun, Ozen Filiz
Department of Medical Biology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey.
Atlas Biotechnology Company, Ankara, Turkey.
Gene. 2017 Aug 30;626:9-13. doi: 10.1016/j.gene.2017.05.013. Epub 2017 May 5.
Familial Mediterranean fever is a common hereditary disease in Turkey. To date, different mutational spectrum of MEFV gene was observed in studies carried out in different regions of Turkey but in most of these studies association of clinical symptoms of FMF to mutant genotypes have not been investigated in details. Here we report the MEFV gene variations in exons 2, 3, 5 and 10 and their relations to major clinical symptoms of FMF in 514 unrelated (245 males and 269 females) Turkish patients. MEFV mutations were found in 45% (n=230) of patients and 55% (n=284) of patients did not have any mutations. One hundred and thirty-seven (60%) patients were heterozygous, 57 (24.7%) patients were compound heterozygous, 33 (14%) patients were homozygous and 3 (1.3%) patients were having a complex genotype. Allele frequencies of MEFV mutations were M694V (48%), E148Q (18%), M680I (15%), V726A (12.5%), P369S (3.3%), R761H (0.9), K695R (0.9), E148V (0.9) and A744S (0.5%). Abdominal pain (76%) and fever (58%) were two most seen complications among patients followed by arthritis (28%) and chest pain (19%). Almost all major clinical symptoms of FMF were higher in patients with one or more M694V or M680I mutant allele. In contrast, patients having E148Q or V726A mutant allele showed fewer clinical FMF symptoms. Patients with P369S have higher abdominal pain, chest pain and fever than expected. Arthritis was high in K695R heterozygous genotype. One hundred and eighteen patients were carrying more than one polymorphic allele. The most common polymorphism was R202Q (13%). In addition, a novel heterozygous polymorphism at 564th nucleotide (C>T) of exon2 were found in 2 patients.
家族性地中海热是土耳其一种常见的遗传性疾病。迄今为止，在土耳其不同地区开展的研究中观察到了MEFV基因不同的突变谱，但在大多数这些研究中，并未详细调查家族性地中海热临床症状与突变基因型之间的关联。在此，我们报告了514名无亲缘关系的（245名男性和269名女性）土耳其患者外显子2、3、5和10中的MEFV基因变异及其与家族性地中海热主要临床症状的关系。45%（n = 230）的患者发现有MEFV突变，55%（n = 284）的患者未发生任何突变。137名（60%）患者为杂合子，57名（24.7%）患者为复合杂合子，33名（14%）患者为纯合子，3名（1.3%）患者具有复杂基因型。MEFV突变的等位基因频率分别为：M694V（48%）、E148Q（18%）、M680I（15%）、V726A（12.5%）、P369S（3.3%）、R761H（0.9%）、K695R（0.9%）、E148V（0.9%）和A744S（0.5%）。腹痛（76%）和发热（58%）是患者中最常见的两种并发症，其次是关节炎（28%）和胸痛（19%）。几乎所有家族性地中海热的主要临床症状在携带一个或多个M694V或M680I突变等位基因的患者中更为常见。相比之下，携带E148Q或V726A突变等位基因的患者表现出较少的家族性地中海热临床症状。携带P369S的患者出现腹痛、胸痛和发热的情况高于预期。K695R杂合基因型的患者关节炎发病率较高。118名患者携带不止一个多态性等位基因。最常见的多态性是R202Q（13%）。此外，在2名患者中发现外显子2第564位核苷酸（C>T）处有一个新的杂合多态性。
