One novel and two uncommon MEFV mutations in Japanese patients with familial Mediterranean fever: a clinicogenetic study
One novel and two uncommon MEFV mutations in Japanese patients with familial Mediterranean fever: a clinicogenetic study
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DOI：
10.1007/s00296-017-3886-z
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Sekijima, Yoshiki
中科院分区：
文献类型：
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作者：
Kishida, Dai;Yazaki, Masahide;Sekijima, Yoshiki
家族性地中海热（FMF）是一种由MEFV基因突变引起的自身炎症性疾病，其特征是反复发作的发热和多浆膜炎。迄今为止，已报告了超过317种MEFV突变，其中只有9种几乎占所有日本FMF患者。因此，罕见MEFV变异的患病率及其临床特征仍不清楚。这项研究确定了以前未报告的日本人群中的MEFV突变，并描述了其临床特征。我们对488例临床疑似FMF的日本患者进行了MEFV基因检测。在这些患者中，我们回顾性分析了3例新的或非常罕见的MEFV突变患者。根据Tel-Hashomer标准对所有患者进行FMF的临床诊断。在MEFV基因中发现了一个新的错义突变（N679 H）和两个罕见突变（T681 I和R410 H）。这些突变在复合杂合或复杂基因型中发现，在外显子1或2中有其他已知的突变。根据临床图像，所有三名患者均表现出典型的FMF症状。在日本人群中可能存在一些由新型或不常见的MEFV变异体引起的FMF患者;因此，需要进行仔细的基因检测以准确诊断这种可治愈的遗传性疾病。
Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the MEFV gene and characterized by recurrent episodes of fever and polyserositis. To date, over 317 MEFV mutations have been reported, only nine of which account for almost all Japanese patients with FMF. Therefore, the prevalence of rare MEFV variants and their clinical characteristics remains unclear. This study identified MEFV mutations previously unreported in the Japanese population and described their clinical features. We performed MEFV genetic testing in 488 Japanese patients with clinically suspected FMF. Of these patients, we retrospectively analyzed three patients with novel or very uncommon MEFV mutations. In all patients, the clinical diagnosis of FMF was made according to Tel-Hashomer's criteria. One novel missense mutation (N679H) and two rare mutations (T681I and R410H) were identified in the MEFV gene. These mutations were found in compound heterozygous or complex genotypes with other known mutations in exons 1 or 2. According to clinical images, all three patients exhibited typical FMF symptoms. A number of patients with FMF caused by novel or uncommon MEFV variants might exist in the Japanese population; therefore, careful genetic testing is required for accurate diagnosis of this curable genetic disorder.