Familial Mediterranean Fever Mutation Analysis

“Heterozygous” means the individual carries 1 copy of a pathogenic variant (mutation) on 1 chromosome. If the pathogenic variant is associated with a recessive disease such as FMF, these individuals are called carriers. Carriers typically do not show symptoms of the disease; however, in some cases, carriers of FMF may be symptomatic.

If a patient has a clinical diagnosis of FMF, they may carry a second MEFV pathogenic variant not tested for in the panel. Additional genetic testing may be available for the patient at another lab. Call Quest Genomics Client Services at 866.GENE.INFO (1.866.436.3463) to discuss next steps for this patient with a genomic science specialist.

“Homozygous” means the individual has 2 copies of the same pathogenic variant, 1 on each chromosome. If the pathogenic variant is associated with a recessive disease such as FMF, these individuals are typically affected; that is, they show symptoms of the disease. A homozygous result supports a clinical diagnosis of FMF.

“Compound heterozygous” means the individual has 1 copy each of 2 different pathogenic variants, 1 on each chromosome. If the pathogenic variants are associated with a recessive disease such as FMF, these individuals are typically affected. A compound heterozygous result supports a clinical diagnosis of FMF. 

Familial mediterranean fever (FMF) is inherited in an autosomal recessive manner. Typically, 2 pathogenic variants within the MEFV gene are required for symptoms to occur. In some cases, carriers (individuals with 1 MEFV pathogenic variant) can be symptomatic.

In most individuals with classic FMF, analysis of the common pathogenic variants confirms the diagnosis with the identification of 2 pathogenic variants. The sensitivity for detecting 2 pathogenic variants is different depending on ethnicity: 70% in Arab populations, 90% in Turkish, Armenian or Ashkenazi Jewish populations, and 95% in North African (Sephardic) Jewish populations. This is because the variants on this assay have different prevalence in these ethnic groups.

In individuals with non-classic FMF or a mild presentation, additional sequence analysis may be considered, but such analysis is not performed at Quest Diagnostics. Please call Quest Genomics Client Services at 866.GENE.INFO (1.866.436.3463) to discuss this scenario with our genomic science specialists.

When the clinical picture suggests FMF and molecular testing is not diagnostic, non-classical variants in the MEFV gene should be considered, as well as other autoinflammatory diseases appropriate to the differential diagnosis.

No, please call Quest Genomics Client Services at 866.GENE.INFO (1.866.436.3463) to discuss this patient with a genomic science specialist. Documentation of the specific MEFV pathogenic variants in the family will be necessary to determine the accuracy of the testing that was performed for the patient.