Department of Pediatrics, SB Tepecik Teaching Hospital, Tepecik, Izmir, Turkey.
Clin Rheumatol. 2012 Mar;31(3):493-501. doi: 10.1007/s10067-011-1876-1. Epub 2011 Nov 5.
The aim of this study was to determine the relationship between clinical findings and the most common mutated alleles of MEFV gene in a childhood population and to determine the sensitivity of the 12-mutation-strip assay test in familial Mediterranean fever (FMF). Records of 452 FMF children living in western Anatolia, Turkey, (12.3 ± 4.7 years mean) were retrospectively reviewed. Of the 408 patients who met the Tel-Hashomer criteria, 364 were classified into two main groups (two-mutant/one-mutant allele) either of which had three subgroups. The two-mutant allele frequency was 51% and one-mutant allele 38%; 1% had complex-mutant alleles and 10% no mutant-alleles. The mean severity score was 8.3 ± 2.5. Most common clinical features were fever (81.9%), abdominal pain (86.3%) and myalgia (58.8%), and the least common ones: diarrhea (1.7%), protracted febrile myalgia (1.2%) and acute orchitis (1.5%). We detected 33 different genotypes of the MEFV gene: the most common mutant allele was M694V followed by symptomatic allele mutation of E148Q. Although not significantly associated with clinical findings, P369S mutation was not rare (7.5%). Phenotype-genotype correlation revealed that patients with two-allele mutations had more severe clinical presentation and high constipation rate (22.5%); 32.6% of patients with M694V/M694V had splenomegaly. Acute orchitis and protracted febrile myalgia as rare clinical findings were more common in M694V homozygotes. Comparisons of clinical findings among patients with one-mutation allele were made for the first time, but no significant association was found. Positive predictive value of strip assay screening for 12 mutations was recorded as 89%. We suggest that whole sequence analysis for supportive diagnosis of FMF should be performed for selected patients only.
本研究旨在确定 MEFV 基因突变在土耳其西部安纳托利亚地区儿童人群中的临床发现之间的关系，并确定 12 突变条带检测试验在家族性地中海热（FMF）中的敏感性。回顾性分析了居住在土耳其西部安纳托利亚地区的 452 名 FMF 儿童（平均年龄 12.3±4.7 岁）的记录。在符合 Tel-Hashomer 标准的 408 名患者中，364 名患者分为两个主要组（双突变/单突变等位基因），每组又分为三个亚组。双突变等位基因频率为 51%，单突变等位基因频率为 38%；1%为复杂突变等位基因，10%无突变等位基因。平均严重程度评分为 8.3±2.5。最常见的临床特征是发热（81.9%）、腹痛（86.3%）和肌痛（58.8%），最不常见的是：腹泻（1.7%）、迁延性发热性肌痛（1.2%）和急性睾丸炎（1.5%）。我们检测到 MEFV 基因的 33 种不同基因型：最常见的突变等位基因是 M694V，其次是 E148Q 症状性等位基因突变。虽然与临床发现无显著相关性，但 P369S 突变并不罕见（7.5%）。表型-基因型相关性显示，双等位基因突变的患者临床表现更严重，便秘发生率更高（22.5%）；32.6%的 M694V/M694V 患者有脾肿大。急性睾丸炎和迁延性发热性肌痛作为罕见的临床发现，在 M694V 纯合子中更为常见。首次对携带单突变等位基因的患者进行了临床发现的比较，但未发现显著相关性。条带检测筛选 12 个突变的阳性预测值记录为 89%。我们建议仅对选定的患者进行支持 FMF 诊断的全序列分析。
