FMF (MEFV) Gene Analysis

What is FMF (MEFV) gene analysis?

Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disease marked by recurrent attacks of fever with abdominal, chest or joint pain. Attacks usually resolve on their own within a few days, and between attacks the person is often completely healthy. The disease is more common in populations around the Mediterranean and is also among the inherited diseases frequently seen in Türkiye. Symptoms usually begin in childhood or young adulthood; diagnosis and follow-up are important because people who are not treated and have frequent attacks may develop amyloidosis in the long term, which can affect the kidneys.

FMF is associated with changes in the MEFV gene, which encodes pyrin, a protein involved in regulating the inflammatory response. The disease is mostly inherited in an autosomal recessive manner; that is, patients usually have changes in both copies of the gene. In MEFV gene analysis, all coding regions of the gene are sequenced in DNA extracted from blood; in this way, the test looks not only for common changes but also for other variants that may be found along the gene.

When is FMF gene analysis ordered?

An FMF diagnosis is made by a doctor based mainly on the symptoms, the characteristics of the attacks and the response to treatment. The genetic test is ordered to support this clinical diagnosis, to help with differential diagnosis in unclear cases or to assess family members.

• Recurrent attacks of fever with no explained cause
• Recurrent abdominal or chest pain accompanied by fever
• Recurrent joint pain and swelling
• Attacks accompanied by redness on the leg
• An FMF diagnosis in the family
• Investigation of the cause of kidney involvement (amyloidosis)

The test can be particularly helpful when attacks begin in childhood and recur frequently. For the siblings and children of people diagnosed with FMF, the doctor may also recommend a genetic assessment depending on symptoms. Noting the dates and duration of attacks and any accompanying symptoms makes it easier for your doctor to evaluate the genetic result together with the clinical picture.

How do you prepare for FMF gene analysis?

No fasting is needed for this test, and the blood sample can be given at any time of day. Because your genetic makeup does not change during or between attacks, the test does not need to coincide with an attack. If you take colchicine or another medication, the genetic result is not affected; do not stop your medication without consulting your doctor.

Genetic tests are performed with informed consent, and genetic counseling is recommended, especially if family planning or testing of relatives is being considered. If you have had a bone marrow transplant, mention this. Our nurse collects your blood sample at your home or workplace. The sample is analyzed at an accredited laboratory.

How are FMF gene analysis results interpreted?

The report states the variants found in the MEFV gene and whether they are present in one or both copies of the gene. Finding disease-associated variants in both copies strongly supports an FMF diagnosis in a person with compatible symptoms. Some variants have a clearer association with the disease, while for others the association is weaker or debated; this distinction matters when interpreting the result.

Finding a single variant, or no variant at all, does not definitively rule out FMF; this can also be seen in people who are clinically diagnosed with FMF and benefit from treatment. On the other hand, some people carry two variants and show no symptoms. For this reason, the test does not make a diagnosis on its own; the result is evaluated by your doctor together with your symptoms and examination findings. Recommending testing to family members and the follow-up plan are also discussed during this assessment.