title: MEFV-Gene analysis in armenian patients with Familial Mediterranean fever: diagnostic value and unfavorable renal prognosis of the M694V homozygous genotype-genetic and therapeutic implications.
abstract: Familial Mediterranean fever (FMF) is a recessively inherited disorder that is common in patients of Armenian ancestry. To date, its diagnosis, which can be made only retrospectively, is one of exclusion, based entirely on nonspecific clinical signs that result from serosal inflammation and that may lead to unnecessary surgery. Renal amyloidosis, prevented by colchicine, is the most severe complication of FMF, a disorder associated with mutations in the MEFV gene. To evaluate the diagnostic and prognostic value of MEFV-gene analysis, we investigated 90 Armenian FMF patients from 77 unrelated families that were not selected through genetic-linkage analysis. Eight mutations, one of which (R408Q) is new, were found to account for 93% of the 163 independent FMF alleles, with both FMF alleles identified in 89% of the patients. In several instances, family studies provided molecular evidence for pseudodominant transmission and incomplete penetrance of the disease phenotype. The M694V homozygous genotype was found to be associated with a higher prevalence of renal amyloidosis and arthritis, compared with other genotypes (P=.0002 and P=.006, respectively). The demonstration of both the diagnostic and prognostic value of MEFV analysis and particular modes of inheritance should lead to new ways for management of FMF-including genetic counseling and therapeutic decisions in affected families.
authors.affiliation: 1Service de Biochimie et de Génétique Moléculaire and the Institut National de la Santé et de la Recherche Médicale (Unité 468), Hôpital, Mondor, France.
authors.forename: C
authors.initials: C
authors.lastname: Cazeneuve
authors.forename: T
authors.initials: T
authors.lastname: Sarkisian
authors.forename: C
authors.initials: C
authors.lastname: Pêcheux
authors.forename: M
authors.initials: M
authors.lastname: Dervichian
authors.forename: B
authors.initials: B
authors.lastname: Nédelec
authors.forename: P
authors.initials: P
authors.lastname: Reinert
authors.forename: A
authors.initials: A
authors.lastname: Ayvazyan
authors.forename: J C
authors.initials: JC
authors.lastname: Kouyoumdjian
authors.forename: H
authors.initials: H
authors.lastname: Ajrapetyan
authors.forename: M
authors.initials: M
authors.lastname: Delpech
authors.forename: M
authors.initials: M
authors.lastname: Goossens
authors.forename: C
authors.initials: C
authors.lastname: Dodé
authors.forename: G
authors.initials: G
authors.lastname: Grateau
authors.forename: S
authors.initials: S
authors.lastname: Amselem
mesh_terms: D000293:Adolescent; D000328:Adult; D001136:Armenia; D002648:Child; D002675:Child, Preschool; D003078:Colchicine / Q000494:pharmacology; D003598:Cytoskeletal Proteins; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006074:Gout Suppressants / Q000494:pharmacology; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin
chemical_list: D003598:Cytoskeletal Proteins; D006074:Gout Suppressants; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin; D003078:Colchicine