A Japanese patient with familial Mediterranean fever associated with compound heterozygosity for pyrin variant E148Q/M694I.

Familial Mediterranean fever (FMF) is an inherited inflammatory disease occurring mainly in Mediterranean and Middle Eastern populations. FMF is caused by mutations in the MEFV gene that encodes pyrin/marenostrin. Here, we report a Japanese female FMF patient with heterozygosity for the compound pyrin E148Q/M694I showing recurrent fever, serositis or delay in skin wound healing. Her father and elder sister were heterozygous for pyrin variant M694I alone and sometimes suffered from mild fever or delay in wound healing, but her mother was heterozygous for pyrin variant E148Q alone and had no symptoms. This suggested that the inheritance of FMF occurred not only in an autosomal recessive manner but also in an autosomal dominant manner in this Japanese family, and the severity of the disease differed among the family members in relation to the mutation. In the treatment of FMF, colchicine, reserpine or prazosin hydrochloride have been reported to prevent the attacks, but, in our patient such drugs were ineffective or caused side effects, and only the anti-allergic drug azelastine was of benefit in relieving the attacks.