Genotype-phenotype and genotype-origin correlations in children with mediterranean fever in Germany - an AID-net study

Familial Mediterranean fever (FMF) is the most inherited common autoinflammatory disease (AID) with mutations in the MEFV (MEditerraneanFeVer) gene. The Mor- and Pras-Score modified for children and C-reactive protein (CRP) were used to assess FMF disease severity in Germany. We evaluate the applicability of the 2 severity scores and the correlations between ethnic origin, phenotype, and genotype. Among 242 children (median 5 age at diagnosis), we detected 431 pyrin mutations and 22 different sequence variants, including one new mutation (p.Gly488Asp). The 5 most ­frequent alterations were p.Met694Val (55.2%), p.Met680lle (11.8%), p.Val726Ala (10%), p.Glu148Gln (7.9%) and p.Met694IIe (2.3%). The prevailing ancestries of 223 cases were Turkish (82.5%) and Lebanese (8.1%). Homozygous p.Met694Val substitution (30.2%) was associated with a more severe disease activity by Mor-Score, as well as with a higher mean CRP (74 mg/l) compared to patients with other mutations. Indeed, Mor- and Pras-Score were inconsistent with each other. A typical distribution of mutations in different ethnic populations was obvious, but not statistically verifiable due to the low number of cases. The homozygous p.Met694Val substitution was associated with a more severe disease activity in our German cohort. The common severity scores were inconsistent in ­children.