title: Mutational spectrum in the MEFV and TNFRSF1A genes in patients suffering from AA amyloidosis and recurrent inflammatory attacks.
abstract: BACKGROUND
  Among hereditary fevers characterized by recurrent attacks of fever and organ localized inflammation, familial Mediterranean fever (FMF), and tumour necrosis factor receptor superfamily 1A (TNFRSF1A) receptor associated periodic syndrome (TRAPS) are diseases with identified genes that can be associated with renal amyloidosis of the AA type. In this study we have characterized FMF and TRAPS genotypes in 38 unrelated patients suffering from amyloidosis AA and recurrent inflammatory attacks.
  
  
  METHODS
  Mutations of the MEFV and TNFRSF1A genes, responsible respectively for FMF and TRAPS, were searched for by amplifying, using polymerase chain reaction (PCR), genomic DNA, and direct sequencing.
  
  
  RESULTS
  Twenty-seven patients (71%) carried mutations in MEFV (22 patients with two mutations, two patients with a single mutation) or TNFRSF1A genes (three patients). Patients with MEFV mutations belonged to the classical at-risk ethnic group for FMF: Sephardic Jews, Turks, Armenians, and Arabs from the Maghreb. The main genotype encountered was M694V/M694V (19/22), one Turkish patient was M680I/M680I, and two Arab patients from the Maghreb were M694I/M694I. We found three Caucasian patients with the C55S, C70Y, R92Q mutations in the TNFRSF1A gene.
  
  
  CONCLUSIONS
  In this series we observed that FMF is the main cause of AA amyloidosis in Sephardic Jews and Turks. MEFV and TNFRSF1A mutations were found in only 6 of 14 Arab patients from the Maghreb. We found three families (one Caucasian and two from Maghreb) with AA amyloidosis without MEFV or TNFRSF1A mutations, suggesting that other genetic cause(s) exist(s). The characterization of mutations in MEFV and TNFRSF1A is important for the therapeutic behaviour of AA amyloidosis associated with inherited recurrent fever.
authors.affiliation: Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dodé
authors.forename: Bouke P C
authors.initials: BP
authors.lastname: Hazenberg
authors.forename: Christophe
authors.initials: C
authors.lastname: Pêcheux
authors.forename: Daniel
authors.initials: D
authors.lastname: Cattan
authors.forename: Bruno
authors.initials: B
authors.lastname: Moulin
authors.forename: Anne
authors.initials: A
authors.lastname: Barthélémy
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gubler
authors.forename: Marc
authors.initials: M
authors.lastname: Delpech
authors.forename: Gilles
authors.initials: G
authors.lastname: Grateau
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D028226:Amyloidosis, Familial / Q000235:genetics*; D015703:Antigens, CD / Q000235:genetics*; D017209:Apoptosis; D003598:Cytoskeletal Proteins; D005006:Ethnicity; D005060:Europe; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D044465:White People
chemical_list: D015703:Antigens, CD; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I