1. Genotype-phenotype and genotype-origin correlations in children with mediterranean fever in Germany - an AID-net study
- Author
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Ulrich Neudorf, Rainer Berendes, Tim Niehues, Tilmann Kallinich, M. Jeske, Elke Lainka, Peter Lohse, T. Berger, J. Berrang, Johannes-Peter Haas, C. Kamlah, G Dueckers, A. Giese, Frank Dressler, P. Lankisch, E. Lilienthal, L. Braunewell, Dirk Föll, Christoph Rietschel, Gerd Horneff, and Dirk Holzinger
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Genotype ,Turkey ,DNA Mutational Analysis ,Familial Mediterranean fever ,Ethnic origin ,Pyrin domain ,Gastroenterology ,Cohort Studies ,Methionine ,Gene Frequency ,Internal medicine ,Germany ,medicine ,Humans ,Registries ,Lebanon ,Child ,Gene ,Alleles ,Genetics ,business.industry ,Homozygote ,Infant ,Valine ,Pyrin ,MEFV ,medicine.disease ,Phenotype ,Familial Mediterranean Fever ,Cytoskeletal Proteins ,C-Reactive Protein ,Amino Acid Substitution ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,Female ,business - 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.
- Published
- 2013