Familial Mediterranean fever in three Japanese patients, and a comparison of the frequency of MEFV gene mutations in Japanese and Mediterranean populations

Abstract

We report on three Japanese patients (two families) with familial Mediterranean fever (FMF), a rare disease in the Far East. Two of the patients (siblings with definite FMF) were heterozygous for both E148Q and M694I, and the remaining patient (with probable FMF and no family history of the disease) was heterozygous for both P369S and R408Q. Although the M694I mutation is less common among Mediterranean populations, it was present in 22 (76%) of 29 Japanese patients with FMF (previously reported cases). We therefore investigated the allele frequency of M694I in the healthy Japanese population, as well as other FMF-causing mutations in exon 10 (M680I, M694V, and V726A) and polymorphisms (E148Q, P369S, and R408Q) of the Mediterranean fever gene (MEFV). The allele frequencies of disease-causing mutations, even M694I, were <0.001. While those of E148Q, P369S, and R408Q were 0.23, 0.057, and 0.054, respectively. Because of the low allele frequencies of disease-causing mutations, FMF is an extremely rare disease among Japanese individuals. However, FMF is an important component of hereditary autoinflammatory syndrome, and a diagnosis of FMF is crucial for the choice of treatment, because of the benefit of colchicine therapy.

Familial Mediterranean Fever in the World

“…In recent years, approximately 100 cases have been reported in Japan (15,16, and Tsuchiya-Suzuki A, et al: unpublished observations). On the other hand, there are countries where FMF has not been found or reported.…”

An Atypical Familial Mediterranean Fever Patient Who Developed Ulcers in the Terminal Ileum and Recurrent Abscess-like Lesions in Multiple Organs

“…FMF is observed most frequently in Jewish, Armenian, Arab, Turkish, and Italian people, and it has been thought to be a rare disease in Japan. However, an increasing number of cases of FMF have been reported in Japan (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Unlike typical FMF cases in endemic areas, some cases in Japan have been sporadic and adult-onset cases.…”

Protracted Febrile Myalgia Syndrome in a Japanese Patient with Fasciitis Detected on MRI

“…The most frequent mutation is homozygosity for M694V (42-83%), although there is one case report describing a patient homozygous for the E148Q mutation (15). While M694V and V726A are the most common mutations in Mediterranean FMF patients (16), they are infrequent in Japanese FMF patients (17,18). The E148Q, P369S and R408Q mutations, which were detected in the present patient, have been reported in patients with atypical FMF in Japan (19).…”