title: Genotype-phenotype and genotype-origin correlations in children with mediterranean fever in Germany - an AID-net study.
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.
authors.affiliation: Pediatric Rheumatology, University Children's Hospital, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Jeske
authors.forename: P
authors.initials: P
authors.lastname: Lohse
authors.forename: T
authors.initials: T
authors.lastname: Kallinich
authors.forename: T
authors.initials: T
authors.lastname: Berger
authors.forename: C
authors.initials: C
authors.lastname: Rietschel
authors.forename: D
authors.initials: D
authors.lastname: Holzinger
authors.forename: C
authors.initials: C
authors.lastname: Kamlah
authors.forename: P
authors.initials: P
authors.lastname: Lankisch
authors.forename: R
authors.initials: R
authors.lastname: Berendes
authors.forename: G
authors.initials: G
authors.lastname: Dueckers
authors.forename: G
authors.initials: G
authors.lastname: Horneff
authors.forename: E
authors.initials: E
authors.lastname: Lilienthal
authors.forename: J P
authors.initials: JP
authors.lastname: Haas
authors.forename: A
authors.initials: A
authors.lastname: Giese
authors.forename: F
authors.initials: F
authors.lastname: Dressler
authors.forename: J
authors.initials: J
authors.lastname: Berrang
authors.forename: L
authors.initials: L
authors.lastname: Braunewell
authors.forename: U
authors.initials: U
authors.lastname: Neudorf
authors.forename: T
authors.initials: T
authors.lastname: Niehues
authors.forename: D
authors.initials: D
authors.lastname: Föll
authors.forename: E
authors.initials: E
authors.lastname: Lainka
mesh_terms: D000293:Adolescent; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D005858:Germany; D006720:Homozygote; D006801:Humans; D007223:Infant; D007861:Lebanon / Q000208:ethnology; D008297:Male; D008715:Methionine / Q000235:genetics; D010641:Phenotype; D000071198:Pyrin; D012042:Registries; D014421:Turkey / Q000208:ethnology; D014633:Valine / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D002097:C-Reactive Protein; D008715:Methionine; D014633:Valine