title: Hereditary renal amyloidosis caused by a new variant lysozyme W64R in a French family.
abstract: BACKGROUND
  The number of proteins with mutations resulting in amyloidosis has continued to increase. Five proteins--transthyretin, fibrinogen alpha-A chain, apolipoprotein AI, lysozyme, apolipoprotein AII, cystatin C and gelsolin--can be associated with hereditary amyloidosis involving the kidney.
  
  
  METHODS
  A French family with a history of autosomal dominant hereditary amyloidosis with early sicca syndrome and nephropathy leading to renal failure after the fifth to the seventh decade was studied. Several tissue specimens obtained from the proband and his relatives were examined. Immunohistochemistry was performed on paraffin embedded sections using the indirect immunoperoxidase technique. We searched for mutations in the five exons and flanking introns of the lysozyme gene.
  
  
  RESULTS
  Amyloid deposits from the bowel, labial salivary gland and kidney were intensively stained by anti-lysozyme antibody. Sequence analysis of lysozyme exon 2 from the affected individuals revealed a nucleotide substitution predicting a substitution of the amino acid at position 64 in the mature protein from tryptophane, an aromatic residue to the cationic residue arginine (W64R).
  
  
  CONCLUSIONS
  We report a novel mutation (W64R) of the lysozyme that is associated with hereditary amyloidosis and prominent nephropathy. Since the treatment of hereditary amyloidosis greatly varies with the nature of the amyloid protein, thorough characterization of the latter is crucial for the management of the disease.
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP)et INSERM EMI 00-05, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Valleix
authors.forename: Séverine
authors.initials: S
authors.lastname: Drunat
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Philit
authors.forename: Daniel
authors.initials: D
authors.lastname: Adoue
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Piette
authors.forename: Dominique
authors.initials: D
authors.lastname: Droz
authors.forename: Brigitte
authors.initials: B
authors.lastname: MacGregor
authors.forename: Denis
authors.initials: D
authors.lastname: Canet
authors.forename: Marc
authors.initials: M
authors.lastname: Delpech
authors.forename: Gilles
authors.initials: G
authors.lastname: Grateau
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence / Q000235:genetics; D005602:France; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009113:Muramidase / Q000097:blood / Q000235:genetics* / Q000652:urine; D010375:Pedigree; D014018:Tissue Distribution
chemical_list: D000682:Amyloid; D009113:Muramidase