title: Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients.
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.
authors.affiliation: Department of Gastroenterology, University of Heidelberg, Bergheimer Strasse 58, 69115 Heidelberg, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Stuehler
authors.forename: Juergen
authors.initials: J
authors.lastname: Reichert
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.forename: Mark
authors.initials: M
authors.lastname: Schaefer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D017668:Age of Onset; D019943:Amino Acid Substitution; D000818:Animals; D002352:Carrier Proteins; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D003062:Codon / Q000235:genetics; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D004283:Dog Diseases / Q000235:genetics; D004285:Dogs; D005091:Exons / Q000235:genetics; D018740:Genetic Heterogeneity; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000453:epidemiology / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D020125:Mutation, Missense; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C480519:COMMD1 protein, human; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003062:Codon; D011506:Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases