Tomiyama N, Higashiuesato Y, Oda T, Baba E, Harada M, Azuma M, Yamashita T, Uehara K, Miyazato A, Hatta K, Ohya Y, Iseki K, Jinno Y, Takishita S
Department of Cardiovascular Medicine, Nephrology and Neurology, University of the Ryukyus, Nishihara, Okinawa, Japan.
Clin Exp Rheumatol. 2008 Jan-Feb;26(1):13-7.
Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of fever with serosal inflammation. FMF gene (MEFV) mutations have been identified primarily in patients from Mediterranean populations. Although several clinical cases have been reported in Japan, there have been few reports to date on mutation analysis. We studied FMF patients and their relatives to examine the clinical and genetic features of this disease in the Japanese population.
Twelve Japanese FMF patients who met the Tel Hashomer criteria and a total of 17 relatives from 5 of 10 families underwent molecular genetic studies to detect MEFV mutations. The characteristics of these Japanese FMF patients and geno-phenotypical correlations were examined.
Almost all of our patients had been suffering for a long time from fever of unknown origin and one patient also had systemic amyloidosis. In our 12 FMF patients, we detected the substitutions E84K, L110P, E148Q, R761H and M694I. We also newly diagnosed 2 relatives as having FMF based on clinical symptoms and the existence of FMF mutations. One patient was homozygous for E148Q, the patient with systemic amyloidosis was a homozygote for M694I and 4 patients from 3 families were compound heterozygotes for E148Q and M694I. Three patients in one family were compound heterozygotes for E148Q, L110P and M694I. There were 3 patients who were heterozygous for E84K, L110P-E148Q or M694I and had no other nucleotide changes in the exons of MEFV. On the other hand, 2 relatives who had never experienced symptoms of FMF were homozygous for L110P-E148Q as well as compound heterozygous for E148Q/E148Q-R761H. E148Q and M694I were the most frequently detected substitutions in our study.
MEFV mutations occur in Japanese FMF patients though FMF is rare in Japan. The identification of MEFV mutations could be a reliable diagnostic test for FMF. The results of genetic analyses on 14 Japanese FMF patients in this study revealed that E148Q and M694I are frequent alleles.
家族性地中海热（FMF）是一种常染色体隐性疾病，其特征为伴有浆膜炎症的反复发热发作。FMF基因（MEFV）突变主要在来自地中海人群的患者中被发现。尽管日本已有数例临床病例报道，但迄今为止关于突变分析的报告却很少。我们对FMF患者及其亲属进行了研究，以探讨该疾病在日本人群中的临床和遗传特征。
12名符合泰尔哈绍梅尔标准的日本FMF患者以及来自10个家庭中5个家庭的总共17名亲属接受了分子遗传学研究，以检测MEFV突变。对这些日本FMF患者的特征以及基因型与表型的相关性进行了研究。
几乎所有患者都长期患有不明原因的发热，一名患者还患有系统性淀粉样变性。在我们的12名FMF患者中，我们检测到了E84K、L110P、E148Q、R761H和M694I替代突变。我们还根据临床症状和FMF突变的存在，新诊断出2名亲属患有FMF。一名患者为E148Q纯合子，患有系统性淀粉样变性的患者为M694I纯合子，来自3个家庭的4名患者为E148Q和M694I的复合杂合子。一个家庭中的3名患者为E148Q、L110P和M694I的复合杂合子。有3名患者为E84K、L110P-E148Q或M694I杂合子，且MEFV外显子中无其他核苷酸变化。另一方面，2名从未出现过FMF症状的亲属为L110P-E148Q纯合子以及E148Q/E148Q-R761H复合杂合子。在我们的研究中，E148Q和M694I是最常检测到的替代突变。
尽管FMF在日本较为罕见，但MEFV突变仍出现在日本FMF患者中。MEFV突变的鉴定可能是FMF的一项可靠诊断测试。本研究中对14名日本FMF患者的遗传分析结果显示，E148Q和M694I是常见等位基因。
