Clinical Trial: Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Genetics and Pathophysiology of Familial Mediterranean Fever and Related Disorders

Brief Summary:

This study is designed to explore the genetics and pathophysiology of diseases presenting with intermittent fever, including familial Mediterranean fever, TRAPS, hyper-IgD syndrome, and related diseases.

The following individuals may be eligible for this study: 1) patients with known or suspected familial Mediterranean fever, TRAPS, hyper-IgD syndrome or related disorders; 2) relatives of these patients; 3) healthy, normal volunteers 7 years of age or older.

Patients will undergo a medical and family history, physical examination, blood and urine tests. Additional tests and procedures may include the following:

  1. X-rays
  2. Consultations with specialists
  3. DNA sample collection (blood or saliva sample) for genetic studies. These might include studies of specific genes, or more complete sequencing of the genome.
  4. Additional blood samples a maximum of 1 pint (450 ml) during a 6-week period for studies of white cell adhesion (stickiness)
  5. Leukapheresis for collecting larger amounts of white cells for study. For this procedure, whole blood is collected through a needle in an arm vein. The blood flows through a machine that separates it into its components. The white cells are removed and the rest of the blood is returned to the body through another needle in the other arm.

Patients may be followed approximately every 6 months to monitor symptoms, adjust medicine dosages, and undergo routine blood and urine tests. They will receive genetic counseling by the study team on the risk of having affected children and be advised of treatment options.

The purpose of this protocol is to study the genetics and pathophysiology of familial Mediterranean fever (FMF) and other related diseases. FMF is a recessively inherited condition characterized by episodes of fever and serositis or synovitis; some patients also develop systemic amyloidosis. Our laboratory has identified the FMF gene and several disease-related mutations. The FMF gene encodes a protein called pyrin that is the prototype of a family of molecules involved in the regulation of apoptosis (cell-death) and inflammation. The precise biochemical mechanism by which these proteins function, and by which mutations cause disease, is still unknown.

There are a number of other conditions, sometimes referred to as autoinflammatory syndromes because of the lack of high-titer autoantibodies or antigen-specific T-cells that are also characterized by episodic inflammation. Seven are caused by mutations in five other genes: the TNF-receptor associated periodic syndrome (TRAPS) is caused by mutations in one of the receptors for tumor necrosis factor (TNF); the hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) is caused by mutations in the gene encoding mevalonate kinase; Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal-onset multisystem inflammatory disease (NOMID) are caused by mutations in the gene encoding cryopyrin, a member of the aforementioned pyrin family of proteins; deficiency of the interleukin-1 receptor antagonist (DIRA) is caused by mutations in the gene that codes for the interleukin-1 receptor antagonist, a protein that helps to regulate levels of the inflammatory cytokine, interleukin-1; and the syndrome of pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) is caused by mutations in PSTPIP1, a protein that binds pyrin. In addition, there are patients with episodic fevers and/or inflammation who do no
Sponsor: National Human Genome Research Institute (NHGRI)

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Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: November 3, 1999
Date Started: March 8, 1994
Date Completion:
Last Updated: April 21, 2017
Last Verified: March 3, 2017