title: The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease.
abstract: BACKGROUND
  It has recently been demonstrated that the Wilson disease (WD) protein directly interacts with the human homolog of the MURR1 protein in vitro and in vivo, and that this interaction is specific for the copper transporter. The aim of the present study was to clarify the role of MURR1 in the pathogenesis of WD as well as in other WD-like disorders of hepatic copper metabolism of unknown origin.
  
  
  METHODS
  Using the single-strand conformation polymorphism (SSCP) method followed by sequencing, we analyzed the 5' untranslated region (UTR) and three exons of the MURR1 gene in three groups of patients: 19 WD: patients in whom no mutations were detected in the ATP7B gene, 53 WD: patients in whom only one mutation in the ATP7B gene was found, and 34 patients in whom clinical and laboratory data suggested a WD-like disorder of hepatic copper metabolism of unknown origin.
  
  
  RESULTS
  We detected in these patients six rare nucleotide substitutions, namely one splice-site consensus sequence and one missense and four silent nucleotide substitutions. All substitutions except one were found in the heterozygous state. No difference in the frequencies of the various substitutions was observed between patients and controls.
  
  
  CONCLUSIONS
  These data suggest that the MURR1 gene and its protein product are unlikely to play a primary role in the pathogenesis of Wilson disease. More extensive studies with larger numbers of clinically homogeneous patients should be carried out to establish whether nucleotide alterations in the MURR1 gene may have a role in causing WD or WD-like disorders or act as modifying factors in the phenotype variability in WD.
authors.affiliation: Institute of Neurogenetics and Neuropharmacology, CNR-Cagliari, Cagliari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Lovicu
authors.forename: Valeria
authors.initials: V
authors.lastname: Dessì
authors.forename: Maria Barbara
authors.initials: MB
authors.lastname: Lepori
authors.forename: Antonietta
authors.initials: A
authors.lastname: Zappu
authors.forename: Lucia
authors.initials: L
authors.lastname: Zancan
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giacchino
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Marazzi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Iorio
authors.forename: Angela
authors.initials: A
authors.lastname: Vegnente
authors.forename: Pietro
authors.initials: P
authors.lastname: Vajro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maggiore
authors.forename: Matilde
authors.initials: M
authors.lastname: Marcellini
authors.forename: Cristiana
authors.initials: C
authors.lastname: Barbera
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kostic
authors.forename: Anna Maria Giulia
authors.initials: AM
authors.lastname: Farci
authors.forename: Antonello
authors.initials: A
authors.lastname: Solinas
authors.forename: Buket
authors.initials: B
authors.lastname: Altuntas
authors.forename: Aysel
authors.initials: A
authors.lastname: Yuce
authors.forename: Nurten
authors.initials: N
authors.lastname: Kocak
authors.forename: Aspasia
authors.initials: A
authors.lastname: Tsezou
authors.forename: Stefano
authors.initials: S
authors.lastname: De Virgiliis
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Georgios
authors.initials: G
authors.lastname: Loudianos
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000235:genetics*; D002352:Carrier Proteins; D027682:Cation Transport Proteins / Q000235:genetics*; D003300:Copper; D000073840:Copper-Transporting ATPases; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011506:Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C480519:COMMD1 protein, human; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D011506:Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases