抽象的な

A rare complex mutation in FMF gene; genetics and treatment decisions in Familial Mediterranean Fever patients

Shailendra Singh, Jyoti Chaudhary & John Meyerhoff

Introduction: FMF is an autosomal-recessive autoinflammatory disease characterized by episodic, self-limiting attacks characterized by fever, abdominal pain, pleurisy, arthritis and erysipelas-like-erythema. Systemic amyloidosis is the most severe manifestation of the disease.

Case: 3 year old patient for evaluation of FMF who was referred because of gastrointestinal symptoms and a paternal family history of FMF. He had a number of gastrointestinal symptoms as an infant up to the age of 8 months, since the age of 1 year the patient had had 2 episodes each lasting 2 months, during which he would be sick every week with fever and severe abdominal pain and vomiting. The patient met the criteria for FMF based on the criteria from the Sheba medical center of Tel Hashomer in Israel. The patient was determined to have rare heterozygous complex mutation with E148Q-P369S-R408Q in cis state. Testing of his parents revealed that he had inherited all of the mutations from his mother despite the paternal familial history of FMF. Since amyloidosis is rare in Ashkenazi families and due to absence of mutations liked with high risk of amyloidosis, it was determined that he did not need chronic colchicine therapy. To best of our knowledge this is the third reported case of FMF with this gene complex and the first reported case in a patient of Shephardic and Ashkenazi Jewish ancestry.

Conclusion: E148Q, P369S and R408Q when present separately are associated with a mild phenotype and incomplete penetrance, but when present together in cis form on same allele may lead to increased penetrance and clinical disease.