Is There Any Difference Between M694V Heterozygote and Non-Exon 10 Mutations on Symptoms Onset and Response to Colchicine Treatment?

Purpose: Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory syndrome throughout the world. The most frequent genotype-phenotype correlation is in a certain part of exon 10, especially M694V mutation. There are also a group of patients with non-exon 10 mutations, who have a similar clinical spectrum of the disease. We aim to investigate the genotype-phenotype differences between M694V heterozygote mutations and non-exon 10 mutations. Materials and methods: Data charts of children (n=431) with FMF from two tertiary hospitals were reviewed. Patients were divided into two groups with regard to having M694V heterozygote or non-exon 10 mutations. Genotype-phenotype features and response to treatment were compared. Results: There were M694V heterozygote mutations in 128 (29.7%) patients and non-exon 10 mutations in 303 (70.3%) patients. The follow-up period was 54.5 (33-105) months. There was no difference between the age of symptoms onset, the age of diagnosis, and the diagnosis delay time. The family history in patients with M694V heterozygote mutation was statistically positive compared to non-exon 10 mutation group (p=0.001). The symptoms of joint involvement as arthritis and PRAS scores were significantly higher in the M694V heterozygote group (p=0.026 and p=0.001). Additionally, biological agent need due to colchicine unresponsiveness was statistically higher in M694V heterozygote group than group with non-exon 10 mutation (p=0.004). Conclusion: There is a significant difference between children with M694V and non-exon 10 mutations, even when the M694V mutation is present in one allele only. Family history with FMF, musculoskeletal symptoms, and unresponsiveness to colchicine are main parameters.