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

Klin Padiatr. 2013 Nov;225(6):325-30. doi: 10.1055/s-0033-1355372. Epub 2013 Oct 24.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Amino Acid Substitution / genetics
  • C-Reactive Protein / metabolism
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cytoskeletal Proteins / genetics
  • DNA Mutational Analysis
  • Familial Mediterranean Fever / diagnosis*
  • Familial Mediterranean Fever / ethnology
  • Familial Mediterranean Fever / genetics*
  • Female
  • Gene Frequency / genetics
  • Genotype*
  • Germany
  • Homozygote
  • Humans
  • Infant
  • Lebanon / ethnology
  • Male
  • Methionine / genetics
  • Phenotype*
  • Pyrin
  • Registries
  • Turkey / ethnology
  • Valine / genetics

Substances

  • Cytoskeletal Proteins
  • MEFV protein, human
  • Pyrin
  • C-Reactive Protein
  • Methionine
  • Valine