Abstract
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.
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DK: conception and design, data collection and analysis, and drafting of the manuscript. MY: conception and design, help in drafting the manuscript. AN: conception and design, help in drafting the manuscript. FN, TK, TU, MI, AO, NW, RE, SK, YSH, and YSE: data collection and interpretation, critically review of the manuscript.
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All authors declare that they have no conflict of interest.
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This work was supported by JSPS KAKENHI (Grant Numbers JP26860447 and JP17K15892).
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Genetic analysis of MEFV was approved by the Institutional Review Board (No. 314; March 8, 2011) in the Shinshu University School of Medicine, Matsumoto, Japan. All patients provided informed consent prior to MEFV genetic testing and agreed to the publication of their clinical characteristics under anonymity.
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Kishida, D., Yazaki, M., Nakamura, A. et al. One novel and two uncommon MEFV mutations in Japanese patients with familial Mediterranean fever: a clinicogenetic study. Rheumatol Int 38, 105–110 (2018). https://doi.org/10.1007/s00296-017-3886-z
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DOI: https://doi.org/10.1007/s00296-017-3886-z