The Cell article explains that mutations in the receptor are responsible for a predisposition to severe inflammation triggered by daily life events such as emotional stress, minor trauma, or for seemingly no apparent reason. This discovery marks the first time that TNF receptor mutations have been tied to an inherited disease. After the FMF gene was identified, it became clear that some families with periodic fevers do not have these FMF mutations. The symptoms most frequently reported by the affected individuals include fever lasting a week or more, accompanied by red and swollen eyes, migratory skin rashes, muscle tenderness, joint pain, and sometimes abdominal or chest pain. An unusually high incidence of inguinal hernia has been noted in affected men.
Some patients also develop amyloidosis, which can be fatal.
One of the best-characterized families is of Irish and Scottish ancestry, and was first described by a research team at the Queen's Medical Centre in Nottingham, England. However, families with similar complaints have now been described in several ethnic groups. Initially, it was not clear whether all of these families had mutations in the same gene or in several related genes. A key advance came about one year ago when two research teams independently identified a region of chromosome 12 associated with susceptibility to this form of periodic fever. One research team was headed by Dr. Michael McDermott, of the Royal London School of Medicine, formerly a postdoctoral fellow in Kastner's lab.