TY - JOUR
T1 - The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis
AU - Müller, Thomas
AU - Van De Sluis, Bart
AU - Zhernakova, Alexandra
AU - Van Binsbergen, Ellen
AU - Janecke, Andreas R.
AU - Bavdekar, Ashish
AU - Pandit, Anand
AU - Weirich-Schwaiger, Helga
AU - Witt, Heiko
AU - Ellemunter, Helmut
AU - Deutsch, Johann
AU - Denk, Helmut
AU - Müller, Wilfried
AU - Sternlieb, Irmin
AU - Tanner, M. Stuart
AU - Wijmenga, Cisca
N1 - Funding Information:
We sincerely thank the affected families for their help and willingness to participate in this study and Jackie Senior for improving the manuscript. We are indebted to Dr. W. Gahl, NIH, for providing fibroblast cell lines of patients 19 and 23. We are grateful for financial support from the Netherlands Organization for Scientific Research (902-23-254) and the International Copper Association (TPT0551).
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Background: Non-Wilsonian hepatic copper toxicosis includes Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis (ETIC) and the non-Indian disease known as idiopathic copper toxicosis (ICT). These entities resemble the hepatic copper overload observed in livers of Bedlington terriers with respect to their clinical presentation and biochemical and histological findings. We recently cloned the gene causing copper toxicosis in Bedlington terriers, MURR1, as well as the orthologous human gene on chromosome 2p13-p16. Aim: To study the human orthologue of the canine copper toxicosis gene as a candidate gene for ICC, ETIC, and ICT. Methods: We sequenced the exons and the intron-exon boundaries of the human MURR1 gene in 12 patients with classical ICC, one patient with ETIC, and 10 patients with ICT to see whether these patients display any mutations in the human orthologue of the canine copper toxicosis gene. Results: No mutations in the MURR1 gene, including the intron-exon boundaries, were identified in a total of 23 patients with non-Wilsonian hepatic copper toxicosis. Conclusions: Our results demonstrate that copper toxicosis in Bedlington terriers is not an animal model for the non-Wilsonian hepatic copper toxicosis described in this study.
AB - Background: Non-Wilsonian hepatic copper toxicosis includes Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis (ETIC) and the non-Indian disease known as idiopathic copper toxicosis (ICT). These entities resemble the hepatic copper overload observed in livers of Bedlington terriers with respect to their clinical presentation and biochemical and histological findings. We recently cloned the gene causing copper toxicosis in Bedlington terriers, MURR1, as well as the orthologous human gene on chromosome 2p13-p16. Aim: To study the human orthologue of the canine copper toxicosis gene as a candidate gene for ICC, ETIC, and ICT. Methods: We sequenced the exons and the intron-exon boundaries of the human MURR1 gene in 12 patients with classical ICC, one patient with ETIC, and 10 patients with ICT to see whether these patients display any mutations in the human orthologue of the canine copper toxicosis gene. Results: No mutations in the MURR1 gene, including the intron-exon boundaries, were identified in a total of 23 patients with non-Wilsonian hepatic copper toxicosis. Conclusions: Our results demonstrate that copper toxicosis in Bedlington terriers is not an animal model for the non-Wilsonian hepatic copper toxicosis described in this study.
KW - Childhood cirrhosis
KW - Copper
KW - Pediatric
UR - http://www.scopus.com/inward/record.url?scp=0037308563&partnerID=8YFLogxK
U2 - 10.1016/S0168-8278(02)00356-2
DO - 10.1016/S0168-8278(02)00356-2
M3 - Article
C2 - 12547404
AN - SCOPUS:0037308563
SN - 0168-8278
VL - 38
SP - 164
EP - 168
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 2
ER -
