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Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients

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Abstract

Wilson disease is a human disorder of copper metabolism resulting in toxic copper accumulation. Patients present with a high clinical variability, even when sharing identical mutations. MURR1, the gene causing canine copper toxicosis in Bedlington terriers, maps to chromosome 2 in humans, a region different to the Wilson gene locus. MURR1 might influence human copper metabolism and the clinical presentation of Wilson disease patients. This study analyzed MURR1 gene sequence in Wilson disease patients and MURR1 gene transcription in selected patients. Mutation analysis of three exons of the MURR1 gene including the intron-exon boundaries was performed in 63 Wilson disease patients by direct sequencing. Of the 63 Wilson patients 19 (30%) had basepair changes in the MURR1 gene. Three intronic base pair changes, one new sequence variation and two known polymorphisms were detected, including the GAT/GAC heterozygous state at codon Asn 164 in 15 (24%) of the analyzed patients. This suggests that GAT/GAC heterozygous state at codon Asn 164 is associated with an earlier onset of disease.

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Abbreviations

PCR :

Polymerase chain reaction

RT :

Reverse transcription

UTR :

Untranslated region

WD :

Wilson disease

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Acknowledgements

We sincerely thank the patients for their help and willingness to participate in this study. We thank Prof. Ferenci, Department of Gastroenterology and Hepatology, Vienna for WD gene analysis and Cathrin Thunert for collecting clinical data and patient specimens.

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Authors and Affiliations

  1. Department of Gastroenterology, University of Heidelberg, Bergheimer Strasse 58, 69115, Heidelberg, Germany

    Bettina Stuehler, Juergen Reichert, Wolfgang Stremmel & Mark Schaefer

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  1. Bettina Stuehler
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  2. Juergen Reichert
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  3. Wolfgang Stremmel
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  4. Mark Schaefer
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Correspondence to Mark Schaefer.

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Stuehler, B., Reichert, J., Stremmel, W. et al. Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients. J Mol Med 82, 629–634 (2004). https://doi.org/10.1007/s00109-004-0557-9

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  • DOI: https://doi.org/10.1007/s00109-004-0557-9

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