incrementalGenetic finding
SAA1 gene polymorphisms identified as independent amyloidosis risk modifier
Familial Mediterranean Fever →Summary
The SAA1 alpha/alpha genotype has been confirmed as an independent risk factor for AA amyloidosis in FMF, beyond MEFV genotype alone. Patients with both M694V homozygosity and SAA1 alpha/alpha genotype face the highest amyloidosis risk, supporting genotype-guided monitoring strategies.
Related genes
MEFVM694V (c.2080A>G, p.Met694Val)
The most common and most severe FMF mutation. Located in exon 10 (B30.2/SPRY domain). Homozygosity associated with earliest onset, highest attack frequency, most arthritis, and greatest risk of AA amyloidosis.MEFVM680I (c.2040G>A/C, p.Met680Ile)
Third most common FMF mutation. Located in exon 10. Homozygosity or compound heterozygosity with M694V associated with severe disease. M680I/M694V combination produces severe phenotype.MEFVV726A (c.2177T>C, p.Val726Ala)
Second most common FMF mutation. Located in exon 10. Heterozygosity generally associated with milder phenotype. However, V726A-E148Q complex allele can be severe.MEFVE148Q (c.442G>C, p.Glu148Gln)
Located in exon 2. Highly controversial — debated whether pathogenic variant or benign polymorphism. Extremely high frequency in general population. When part of a complex allele with V726A, significantly increases disease severity.MEFVM694I (c.2082G>A/C, p.Met694Ile)
Located in exon 10. Fifth founder mutation. Homozygosity associated with severe disease. M694I/M694I genotype identified as a specific risk factor for AA amyloidosis in Algerian patients.SAA1SAA1 alpha/alpha genotype
The SAA1 alpha/alpha genotype is associated with a sevenfold increase in incidence of renal amyloidosis, especially in patients homozygous for M694V. SAA1 beta and gamma alleles appear protective against amyloidosis.More from Familial Mediterranean Fever
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ID: familial-mediterranean-fever-update-3Type: genetic_findingImpact: incremental