Protocol Number: 94-AR-0105

Title:

Genetics and Pathophysiology of Familial Mediterranean Fever and Related Disorders

Number:

94-AR-0105

Summary:

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

The following individuals may be eligible for this study: 1) patients 5 years of age and older with known or suspected familial Mediterranean fever, TRAPS, hyper-IgD syndrome or related disorders; 2) relatives of these patients; 3) healthy, normal volunteers 18 years of age or older; and 4) healthy patients with gout 18 years of age or older who are taking colchicine.

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 sample or cells obtained from a brushing of the inside of the cheek) for genetic studies, if this has not already been done.

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.

6. Bone marrow aspiration to study white cells early in their development. This procedure will be requested of only a few patients. An area of skin on the back is numbed, a needle is inserted into a pelvic bone, and a small amount of bone marrow is withdrawn.

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

Participating relatives will undergo a medical and family history, possibly with a review of medical records, physical examination, blood and urine tests. Additional procedures may include a 24-hour urine collection, X-rays, and consultations with medical specialists. A DNA sample (blood or cheek swabbing) will also be collected for genetic studies. Additional blood samples of no more than 1 pint during a 6-week period may be requested for studies of white cell adhesion (stickiness).

Relatives who have familial Mediterranean fever, TRAPS, or hyper-IgD syndrome will receive the same follow-up and counseling as described for patients above.

Normal volunteers and patients with gout will have a brief health interview and check of vital signs (blood pressure and pulse) and will provide a blood sample (up to 90 ml, or 6 tablespoons). Additional blood samples of no more than 1 pint over a 6-week period may be requested in the future.

Sponsoring Institute:

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Individuals referred to the NIH with a possible diagnosis of FMF, TRAPS, HIDS, MWS, FCAS, PAPA, PFAPA, or other unexplained febrile illnesses.

Individuals over 1 year of age may be seen for initial evaluation, genetic studies, and research blood specimens, or may send blood or buccal samples for genetic testing only.

We place the following age restrictions on other studies:

Leukapheresis will only be performed on individuals over the age of 18 years;

Brief interruption of ongoing therapy for research blood sampling will only be proposed to individuals over the age of 18 years;

Research bone marrow aspirations and biopsies will only be performed on individuals over the age of 18 years.

Family members of individuals: Individuals over 1 year of age may be seen for initial evaluations, genetic studies, or research blood specimens, or may send blood or buccal samples for genetic testing only. Unaffected family members will not be asked to undergo leukapheresis, interruption of ongoing therapy, or bone marrow aspirations and biopsies.

Controls for cellular, biochemical, or molecular assays: All these individuals will be required to be over the age of 18, not pregnant, and otherwise in good health.

EXCLUSION CRITERIA

Inability to provide informed consent or, in the case of minors, unavailability of a parent or guardian.

Presence of any medical condition that would, in the opinion of the investigators confuse the interpretation of the study.

Special Instructions: Currently Not Provided

Keywords:

Familial Mediterranean Fever

Genetics

Integrins

Positional Cloning

Linkage

Periodic Disease

Family Studies

Recruitment Keywords:

None

Conditions:

Periodic Disease

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever - The International FMF Consortium

Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes

TNFRSF1A mutations and autoinflammatory syndromes

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

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