title: Mutational analysis of the PRYSPRY domain of pyrin and implications for familial mediterranean fever (FMF).
abstract: Familial Mediterranean fever (FMF) is an autosomal, recessively inherited disease, characterized by recurrent fever and serositis that affects mainly patients of the Mediterranean basin. The gene responsible for FMF, named MEFV, was cloned and several missense mutations were found to be responsible for the disease. Based on a recent molecular analysis of MEFV gene mutations in 43 patients from Crete aiming to correlate specific genotypes and clinical manifestations of FMF, we were prompted to construct a three-dimensional model (3-D model) of the PRYSPRY domain of pyrin. The majority of the known MEFV mutations located on this domain have been classified, according to disease severity, and localized on this 3-D model. The functional consequences of these mutations and their implications on disease severity are discussed. Moreover, we report a putative novel missense mutation, S702C, which we identified in exon 10 of the MEFV gene and localized on the constructed 3-D model.
authors.affiliation: Department of Internal Medicine, University of Crete, Heraklion, Greece. guolielmos@med.uoc.gr
authors.forename: G N
authors.initials: GN
authors.lastname: Goulielmos
authors.forename: E
authors.initials: E
authors.lastname: Fragouli
authors.forename: I
authors.initials: I
authors.lastname: Aksentijevich
authors.forename: P
authors.initials: P
authors.lastname: Sidiropoulos
authors.forename: D T
authors.initials: DT
authors.lastname: Boumpas
authors.forename: E
authors.initials: E
authors.lastname: Eliopoulos
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics*; D010505:Familial Mediterranean Fever / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary / Q000235:genetics; D000071198:Pyrin
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin