Impact of MEFV genotype in Caucasian children with periodic fever
Pediatric Rheumatology volume 9, Article number: P302 (2011)
Despite FMF is considered an autosomal recessive disease caused by mutations of MEFV, one third of patients carries one mutation only.
To analyze the actual impact of MEFV mutations in children with periodic fever.
113 caucasian patients carrying MEFV mutations (46 with mutations in two alleles, 67 heterozygous) and 205 genetically negative patients for MEFV, TNFSF1A and MEFV (70% with a PFAPA phenotype) were analyzed. The following groups were considerd: patients with: i) 2 high penetrance mutations (M694V, M694I, M680I), ii) 1 high, 1 low penetrance mutation, iii) 2 low penetrance mutations, iv) 1 high penetrance mutation, v) one low penetrance mutation, vi) genetically negative.
Patients with two mutations displayed a higher prevalence of chest pain (p = 0.001), pleurisy (p = 0.003) and severe abdominal pain (p = 0.002) in respect to heterozygous patients, which clinical phenotype was more similar to that presented by genetically negative patients, with an higher prevalence of erythematous (p = 0.01) and exudative ( p = 0.009) pharyngitis, enlarged cervical lymph nodes (p = 0.002). The frequency of “FMF-like symptoms” decreases from patients carrying two high penetrance mutations towards patients with a single low penetrance mutation with a specular increase of “PFAPA-like symptoms” (Figure 1).
The present study shows a dosage effect of MEFV mutations not consistent with a pure autosomal recessive disorder. A dominant negative or gain of function effects or variants of still unidentified modifier genes may influence the presence of a FMF phenotype in heterozygous patients.
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Federici, S., Calcagno, G., Finetti, M. et al. Impact of MEFV genotype in Caucasian children with periodic fever. Pediatr Rheumatol 9 (Suppl 1), P302 (2011). https://doi.org/10.1186/1546-0096-9-S1-P302