Table 1.

Recommendations for familial Mediterranean fever (FMF) genetic diagnosis [adapted from Ref. (8)].

Recommendation	Strength of evidence
1. FMF is a clinical diagnosis, which can be supported but not excluded by genetic testing	B
2. Consider patients homozygous for M694V at risk of developing, with very high probability, a severe phenotype	B
3. FMF patients carrying two of the common mutated alleles (homozygotes or compound heterozygotes), especially for M694V mutation or mutations at position 680–694 on exon 10, must be considered at risk of having a more severe disease	B
4. The E148Q variant is common, of unknown pathogenic significance, and as the only MEFV variant does not support the diagnosis of FMF	B
5. Patients homozygous for M694V mutation are at risk of early onset disease	C
6. Individuals homozygous for M694V who are not reporting symptoms should be evaluated and followed closely in order to consider therapy	A
7. For individuals with two pathogenic mutations for FMF who do not report symptoms, if there are risk factors for AA amyloidosis (such as the country, family history, and persistently elevated inflammatory markers, particularly serum amyloid A protein), close follow-up should be started and treatment considered	B
8. Consultation with an autoinflammatory disease specialist may be helpful in order to aid in the indication and interpretation of the genetic testing and diagnosis	C