Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020;59(11):1373-1378.
doi: 10.2169/internalmedicine.3778-19. Epub 2020 Jun 1.

Clinical and Genetic Analysis of 22 Japanese Patients with Familial Mediterranean Fever: An Examination of MEFV and 10 Other Genes Related to Autoinflammatory Syndromes

Kyoko Fujimoto  1 , Yukiko Hidaka  1 , Takuma Koga  1 , Shinjiro Kaieda  1 , Satoshi Yamasaki  2 , Munetoshi Nakashima  2 , Tomoaki Hoshino  1 , Hiroaki Ida  1
Affiliations

Clinical and Genetic Analysis of 22 Japanese Patients with Familial Mediterranean Fever: An Examination of MEFV and 10 Other Genes Related to Autoinflammatory Syndromes

Kyoko Fujimoto et al. Intern Med. 2020.

Abstract

Objective Familial Mediterranean Fever (FMF) is the most frequent autoinflammatory syndrome, and its frequency is reported to be increasing in Japan. We studied the clinical features and genetic background of patients with FMF in our hospital. Methods We analyzed the clinical features and genomic variants of MEFV, as well as 10 genes related to other autoinflammatory syndromes, in 22 Japanese patients with FMF. A genetic analysis was performed with a next generation sequencer. Results The patients were classified into the typical FMF (n=16) and atypical FMF (n=6) groups. Fever, abdominal pain, thoracic pain, and arthralgia were observed in 22, 12, 8, and 10 patients, respectively. MEFV variants were found in 19 patients (86.4%). Two cases had no MEFV variants and one case only had a variant in the 3' untranslated region (3'-UTR) of MEFV. Genomic variants were found in genes other than MEFV in 7 patients (31.8%); however, none met the diagnostic criteria for autoinflammatory syndromes with disease-related gene variants, and all were classified as typical FMF. Moreover, none of the 6 patients with atypical FMF had any variants among the 10 disease-related genes. All cases in which the onset occurred before 20 years of age were classified as typical FMF. Conclusion The clinical features of FMF recorded in our hospital coincided with those from the Japanese national epidemiological survey of FMF in Japan. More than 30% of the patients with FMF had non-MEFV genes, related to other autoinflammatory syndromes, thereby suggesting that variants of these genes may act as a disease-modifier in FMF.

Keywords: MEFV; autoinflammatory syndrome; familial mediterranean fever.

PubMed Disclaimer

Conflict of interest statement

The authors state that they have no Conflict of Interest (COI).

References

    1. The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 90: 797-807, 1997. - PubMed
    1. Touitou I. The spectrum of Familial Mediterranean Fever (FMF) mutations. Eur J Hum Genet 9: 473-483, 2001. - PubMed
    1. Migita K, Izumi Y, Jiuchi Y, et al. Familial Mediterranean fever is no longer a rare disease in Japan. Arthritis Res Ther 18: 175, 2016. - PMC - PubMed
    1. Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40: 1879-1885, 1997. - PubMed
    1. Ueda N, Ida H, Washio M, et al. Clinical and genetic features of patients with TNFRSF1A variants in Japan: findings of a nationwide survey. Arthritis Rheumatol 68: 2760-2771, 2016. - PubMed

MeSH terms