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         headline:The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease
         description: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. 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. 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. 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.
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      headline:The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease
      description: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. 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. 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. 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.
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      pageEnd:587
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         liver
         copper accumulation
         mutation analysis
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         Abdominal Surgery
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         name:Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
         type:PostalAddress
      name:University of Thessaly
      address:
         name:Department of Biology, Medical School, University of Thessaly, Larissa, Greece
         type:PostalAddress
      name:University of Cagliari
      address:
         name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
         type:PostalAddress
      name:CNR-Cagliari
      address:
         name:Institute of Neurogenetics and Neuropharmacology, CNR-Cagliari, Cagliari, Italy
         type:PostalAddress
      name:CNR-Cagliari
      address:
         name:Institute of Neurogenetics and Neuropharmacology, CNR-Cagliari, Cagliari, Italy
         type:PostalAddress
      name:University of Cagliari
      address:
         name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
         type:PostalAddress
      name:Regional Thalassemia Hospital
      address:
         name:Regional Thalassemia Hospital, Cagliari, Italy
         type:PostalAddress
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Person:
      name:Mario Lovicu
      affiliation:
            name:CNR-Cagliari
            address:
               name:Institute of Neurogenetics and Neuropharmacology, CNR-Cagliari, Cagliari, Italy
               type:PostalAddress
            type:Organization
      name:Valeria Dessì
      affiliation:
            name:University of Cagliari
            address:
               name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
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      name:Maria Barbara Lepori
      affiliation:
            name:University of Cagliari
            address:
               name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
               type:PostalAddress
            type:Organization
      name:Antonietta Zappu
      affiliation:
            name:University of Cagliari
            address:
               name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
               type:PostalAddress
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      name:Lucia Zancan
      affiliation:
            name:University of Padua
            address:
               name:Department of Pediatrics, University of Padua, Padua, Italy
               type:PostalAddress
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      name:Raffaella Giacchino
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            name:Health Direction G. Gaslini Children's Hospital
            address:
               name:Infectious Diseases Unit, Health Direction G. Gaslini Children's Hospital, Genova, Italy
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            address:
               name:Department of Pediatrics, University of Naples Federico II, Napoli, Italy
               type:PostalAddress
            type:Organization
      name:Angela Vegnente
      affiliation:
            name:University of Naples Federico II
            address:
               name:Department of Pediatrics, University of Naples Federico II, Napoli, Italy
               type:PostalAddress
            type:Organization
      name:Pietro Vajro
      affiliation:
            name:University of Naples Federico II
            address:
               name:Department of Pediatrics, University of Naples Federico II, Napoli, Italy
               type:PostalAddress
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      name:Giuseppe Maggiore
      affiliation:
            name:University of Pisa
            address:
               name:Department of Procreative Medicine and Child Development, Division of Pediatrics, University of Pisa, Pisa, Italy
               type:PostalAddress
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      name:Matilde Marcellini
      affiliation:
            name:Children's Hospital Bambino Gesu
            address:
               name:Department of Liver Disease, Children's Hospital Bambino Gesu, Rome, Italy
               type:PostalAddress
            type:Organization
      name:Cristiana Barbera
      affiliation:
            name:University Hospital ‘Regina Margherita’
            address:
               name:Paediatric Gastroenterology Department, University Hospital ‘Regina Margherita’, Turin, Italy
               type:PostalAddress
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      name:Vladimir Kostic
      affiliation:
            name:Institute of Neurology-Clinical Center of Serbia
            address:
               name:Institute of Neurology-Clinical Center of Serbia, Belgrade, Yugoslavia
               type:PostalAddress
            type:Organization
      name:Anna Maria Giulia Farci
      affiliation:
            name:University of Cagliari
            address:
               name:Department of Medical Internal Sciences, University of Cagliari, Cagliari, Italy
               type:PostalAddress
            type:Organization
      name:Antonello Solinas
      affiliation:
            name:University of Sassari
            address:
               name:Department of Internal Medicine, University of Sassari, Sassari, Italy
               type:PostalAddress
            type:Organization
      name:Buket Altuntas
      affiliation:
            name:Gazi University
            address:
               name:Department of Pediatric Gastroenterology, Gazi University, Ankara, Turkey
               type:PostalAddress
            type:Organization
      name:Aysel Yuce
      affiliation:
            name:Hacettepe University Faculty of Medicine
            address:
               name:Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
               type:PostalAddress
            type:Organization
      name:Nurten Kocak
      affiliation:
            name:Hacettepe University Faculty of Medicine
            address:
               name:Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
               type:PostalAddress
            type:Organization
      name:Aspasia Tsezou
      affiliation:
            name:University of Thessaly
            address:
               name:Department of Biology, Medical School, University of Thessaly, Larissa, Greece
               type:PostalAddress
            type:Organization
      name:Stefano De Virgiliis
      affiliation:
            name:University of Cagliari
            address:
               name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
               type:PostalAddress
            type:Organization
      name:Antonio Cao
      affiliation:
            name:CNR-Cagliari
            address:
               name:Institute of Neurogenetics and Neuropharmacology, CNR-Cagliari, Cagliari, Italy
               type:PostalAddress
            type:Organization
      name:Georgios Loudianos
      affiliation:
            name:CNR-Cagliari
            address:
               name:Institute of Neurogenetics and Neuropharmacology, CNR-Cagliari, Cagliari, Italy
               type:PostalAddress
            type:Organization
            name:University of Cagliari
            address:
               name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
               type:PostalAddress
            type:Organization
            name:Regional Thalassemia Hospital
            address:
               name:Regional Thalassemia Hospital, Cagliari, Italy
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Institute of Neurogenetics and Neuropharmacology, CNR-Cagliari, Cagliari, Italy
      name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
      name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
      name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
      name:Department of Pediatrics, University of Padua, Padua, Italy
      name:Infectious Diseases Unit, Health Direction G. Gaslini Children's Hospital, Genova, Italy
      name:Infectious Diseases Unit, Health Direction G. Gaslini Children's Hospital, Genova, Italy
      name:Department of Pediatrics, University of Naples Federico II, Napoli, Italy
      name:Department of Pediatrics, University of Naples Federico II, Napoli, Italy
      name:Department of Pediatrics, University of Naples Federico II, Napoli, Italy
      name:Department of Procreative Medicine and Child Development, Division of Pediatrics, University of Pisa, Pisa, Italy
      name:Department of Liver Disease, Children's Hospital Bambino Gesu, Rome, Italy
      name:Paediatric Gastroenterology Department, University Hospital ‘Regina Margherita’, Turin, Italy
      name:Institute of Neurology-Clinical Center of Serbia, Belgrade, Yugoslavia
      name:Department of Medical Internal Sciences, University of Cagliari, Cagliari, Italy
      name:Department of Internal Medicine, University of Sassari, Sassari, Italy
      name:Department of Pediatric Gastroenterology, Gazi University, Ankara, Turkey
      name:Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
      name:Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
      name:Department of Biology, Medical School, University of Thessaly, Larissa, Greece
      name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
      name:Institute of Neurogenetics and Neuropharmacology, CNR-Cagliari, Cagliari, Italy
      name:Institute of Neurogenetics and Neuropharmacology, CNR-Cagliari, Cagliari, Italy
      name:Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy
      name:Regional Thalassemia Hospital, Cagliari, Italy
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