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The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease |
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| Authors: | Mario Lovicu Valeria Dessì Maria Barbara Lepori Antonietta Zappu Lucia Zancan Raffaella Giacchino Maria Grazia Marazzi Raffaele Iorio Angela Vegnente Pietro Vajro Giuseppe Maggiore Matilde Marcellini Cristiana Barbera Vladimir Kostic Anna Maria Giulia Farci Antonello Solinas Buket Altuntas Aysel Yuce Nurten Kocak Aspasia Tsezou Stefano De Virgiliis Antonio Cao Georgios Loudianos |
| Institution: | (1) Institute of Neurogenetics and Neuropharmacology, CNR-Cagliari, Cagliari, Italy;(2) Department of Biomedical Sciences and Biotechnologies, University of Cagliari, Cagliari, Italy;(3) Department of Pediatrics, University of Padua, Padua, Italy;(4) Infectious Diseases Unit, Health Direction G. Gaslini Children's Hospital, Genova, Italy;(5) Department of Pediatrics, University of Naples Federico II, Napoli, Italy;(6) Department of Procreative Medicine and Child Development, Division of Pediatrics, University of Pisa, Pisa, Italy;(7) Department of Liver Disease, Children's Hospital Bambino Gesu, Rome, Italy;(8) Paediatric Gastroenterology Department, University Hospital ‘Regina Margherita’, Turin, Italy;(9) Institute of Neurology-Clinical Center of Serbia, Belgrade, Yugoslavia;(10) Department of Medical Internal Sciences, University of Cagliari, Cagliari, Italy;(11) Department of Internal Medicine, University of Sassari, Sassari, Italy;(12) Department of Pediatric Gastroenterology, Gazi University, Ankara, Turkey;(13) Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey;(14) Department of Biology, Medical School, University of Thessaly, Larissa, Greece;(15) Regional Thalassemia Hospital, ASL 8, Cagliari, Via Jenner s/n, 09121 Cagliari, Italy |
| 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. |
| Keywords: | MURR1 liver copper accumulation mutation analysis Wilson disease |
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