Demirkaya Erkan, Tunca Yusuf, Gok Faysal, Ozen Seza, Gul Davut
Department of Pediatrics, Gülhane Military Medical Academy, Etlik, Ankara, Turkey.
Clin Rheumatol. 2008 Jun;27(6):729-32. doi: 10.1007/s10067-007-0780-1. Epub 2007 Nov 14.
Familial Mediterranean fever (FMF) is an autosomal-recessive disease. It is characterized by recurring fever, abdominal pain, and serositis. The Mediterranean fever (MEFV) gene is localized on 16p13.3 and more than 35 mutations have been described to date. There are some differences in the gene mutations of FMF in the various ethnic groups. The aim of this study is to determine the frequency of the mutations which has been reported comparatively rare, to define the most effective mutation set, and to select the most suitable DNA analysis system for Turkish FMF patients. Mutations in 330 Turkish FMF patients with typical phenotypes from various regions of Turkey were evaluated for the research purposes. These patients were analyzed for six MEFV gene mutations by the NanoChip Molecular Genetics Workstation. The most frequent mutation was M694V, identified in 50.00% of the alleles examined; M680I followed with 14.10% and V726A--9.70%. Consequently, we determined that R761H (n = 23; 3.48%) was the most frequent rare mutations in Turkish FMF patients. Frequency of the rare mutations were R761H (3.48%), E148Q (1.36%), and M694I (1.21%). All of these mutations were in the compound heterozygote state. Our study showed that R761H mutations were higher than it has been reported in literature until now and were mainly associated with M694V. We suggest that mutation R761H should be included in the mutation scanning analysis researches or considered if the patient has M694V/? mutation especially in Turkish FMF patients. Larger serial studies need to be done to investigate the rate and coexistence of these mutations.
家族性地中海热（FMF）是一种常染色体隐性疾病。其特征为反复发热、腹痛和浆膜炎。地中海热（MEFV）基因定位于16p13.3，迄今已描述了35种以上的突变。不同种族的FMF基因突变存在一些差异。本研究的目的是确定相对罕见的已报道突变的频率，定义最有效的突变组合，并为土耳其FMF患者选择最合适的DNA分析系统。为研究目的，对来自土耳其不同地区的330例具有典型表型的土耳其FMF患者的突变进行了评估。通过纳米芯片分子遗传学工作站对这些患者的6种MEFV基因突变进行了分析。最常见的突变是M694V，在所检测的等位基因中占50.00%；其次是M680I，占14.10%，V726A占9.70%。因此，我们确定R761H（n = 23；3.48%）是土耳其FMF患者中最常见的罕见突变。罕见突变的频率为R761H（3.48%）、E148Q（1.36%）和M694I（1.21%）。所有这些突变均处于复合杂合子状态。我们的研究表明，R761H突变高于迄今文献报道的水平，且主要与M694V相关。我们建议，在突变扫描分析研究中应纳入R761H突变，或者在患者具有M694V/?突变时考虑该突变，尤其是在土耳其FMF患者中。需要进行更大规模的系列研究来调查这些突变的发生率和共存情况。
