Ayaz N A, Ozen S, Bilginer Y, Ergüven M, Taşkiran E, Yilmaz E, Beşbaş N, Topaloğlu R, Bakkaloğlu A
Pediatric Nephrology and Rheumatology Unit, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Rheumatology (Oxford). 2009 Jan;48(1):23-5. doi: 10.1093/rheumatology/ken409. Epub 2008 Nov 4.
Autoinflammatory diseases constitute a large spectrum of monogenic diseases like FMF or cryopyrin-associated periodic syndromes (CAPS) and complex genetic trait diseases such as systemic onset juvenile idiopathic arthritis (SoJIA). An increased rate of MEFV mutations has been shown among patients with PAN and HSP, in populations where FMF is frequent. The aim of the study is to search for MEFV mutations in our patients with SoJIA and see whether these mutations had an effect on disease course or complications.
Thirty-five children with the diagnosis of SoJIA were screened for 12 MEFV mutations. The control data were obtained from a previous study of our centre determining the carrier frequency in Turkish population.
Two patients were homozygous and three patients were heterozygous for the M694V mutation. One patient was a compound heterozygote for the M680I/V726A mutations. Heterozygous V726A mutation was found in one patient. The overall mutation frequency of patients was 14.28%. This figure had been compared with the previously published rate of disease-causing mutations in this country, which is 5%. Disease-causing mutations were found to be significantly more frequent in the SoJIA patients than the population (P < 0.01). Among these, M694V was the leading mutation with a frequency of 10% in SoJIA. Six patients carrying MEFV mutations were among the most resistant cases requiring biological therapy.
SoJIA patients had a significantly higher frequency of MEFV mutations but clinical studies with large number of patients are needed to confirm the association of MEFV mutations with SoJIA and its course.
自身炎症性疾病包括一大类单基因疾病，如家族性地中海热（FMF）或冷吡啉相关周期性综合征（CAPS），以及复杂遗传性状疾病，如全身型幼年特发性关节炎（SoJIA）。在FMF常见的人群中，结节性多动脉炎（PAN）和过敏性紫癜（HSP）患者中已显示MEFV突变率增加。本研究的目的是在我们的SoJIA患者中寻找MEFV突变，并观察这些突变是否对疾病进程或并发症有影响。
对35例诊断为SoJIA的儿童进行12种MEFV突变的筛查。对照数据来自我们中心之前一项确定土耳其人群携带者频率的研究。
两名患者为M694V突变的纯合子，三名患者为杂合子。一名患者为M680I/V726A突变的复合杂合子。在一名患者中发现杂合子V726A突变。患者的总体突变频率为14.28%。该数字与该国先前公布的致病突变率（5%）进行了比较。发现SoJIA患者中致病突变的频率明显高于总体人群（P<0.01）。其中，M694V是主要突变，在SoJIA中的频率为10%。六名携带MEFV突变的患者是最需要生物治疗的耐药病例。
SoJIA患者中MEFV突变的频率明显更高，但需要大量患者的临床研究来证实MEFV突变与SoJIA及其病程的关联。
