Wilson disease: New insights into pathogenesis, diagnosis, and future therapy

Current Gastroenterology Reports

Volumn 7, Issue 1, 2005, Pages 26-31

  Schilsky, Michael L ^a  

^a WEILL CORNELL MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE; CATION TRANSPORT PROTEIN; COPPER TRANSPORTING ATPASES; COPPER-TRANSPORTING ATPASES; PENICILLAMINE;

CELL TRANSPLANTATION; FEMALE; FORECASTING; GENE THERAPY; GENETIC PREDISPOSITION; GENETICS; HOSPITALIZATION; HUMAN; LIVER CELL; LIVER TRANSPLANTATION; MALE; METHODOLOGY; MORTALITY; PROGNOSIS; REVIEW; RISK ASSESSMENT; SURVIVAL; TRANSPLANTATION; TREATMENT OUTCOME; WILSON DISEASE;

ADENOSINE TRIPHOSPHATASES; CATION TRANSPORT PROTEINS; CELL TRANSPLANTATION; FEMALE; FORECASTING; GENE THERAPY; GENETIC PREDISPOSITION TO DISEASE; HEPATOCYTES; HEPATOLENTICULAR DEGENERATION; HUMANS; LIVER TRANSPLANTATION; MALE; PENICILLAMINE; PROGNOSIS; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; SURVIVAL ANALYSIS; TREATMENT OUTCOME;

EID: 22144447718     PISSN: 15228037     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11894-005-0062-5     Document Type: Review

References (30)

1. Bowcock AM, Farrer LA, Hebert JM, et al.: Eight closely linked loci place the Wilson disease locus within 13q14-q21. Am J Hum Genet 1988, 43: 664-674. Initial studies showing localization to chromosome 13 that set the stage for identification of the gene for Wilson disease (see [2-4]).
2. Petrukhin K, Lutsenko S, Chernov I, et al.: Characterization of the Wilson disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing, and structure/function predictions. Hum Mol Genet 1994, 3: 1647-1656.
3. Thomas GR, Forbes JR, Roberts EA, et al.: The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet 1995, 9: 210-217.
4. Yamaguchi Y, Heiny ME, Gitlin JD: Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease. Biochem Biophys Res Commun 1993, 197: 271-277.
5. Schilsky ML, Stockert RJ, Sternlieb I: Pleiotropic effect of LEC mutation: A rodent model of Wilson's disease. Am J Physiol. 1994, 266: G907-G913. These studies showed that the defect in the LEC rat is in biliary copper excretion, and not a failure of lysosomal delivery to bile. The dual function of the ATP7B gene to transport copper into endosomal/lysosomal vesicles and to Golgi for copper incorporation into ceruloplasmin was demonstrated.
6. Huster D, Hoppert M, Lutsenko S, et al.: Defective cellular localization of mutant ATP7B in Wilson's disease patients and hepatoma cell lines. Gastroenterology 2003, 124: 335-345. The failure of some disease-specific mutants to localize properly to the trans-Golgi was demonstrated by transfection of liver cell lines. These data show the importance of proper cellular localization for ATP7B function.
7. Gitlin JD: Wilson disease. Gastroenterology 2003, 125: 1868-1877. Excellent review on hepatocellular copper metabolism.
8. La Fontaine SL, Firth SD, Camakaris J, et al.: Correction of the copper transport defect of Menkes patient fibroblasts by expression of the Menkes and Wilson ATPases. J Biol Chem 1998, 273: 31375-31380.
9. Cater MA, Forbes J, La Fontaine S, et al.: Intracellular trafficking of the human Wilson protein: The role of the six N-terminal metal-binding sites. Biochem J 2004, 380: 805-813.
10. Walker JM, Huster D, Ralle M, et al.: The N-terminal metal-binding site 2 of the Wilson's disease protein plays a key role in the transfer of copper from Atox1. Biochem J 2004, 380: 805-813.
11. Hsi G, Cox DW: A comparison of the mutation spectra of Menkes disease and Wilson disease. Hum Genet 2004, 114: 165-172. A review of the common mutations of ATP7B and a comparison with defects in ATP7A found in Menkes disease.
12. Schiefermeier M, Kollegger H, Madl C, et al.: The impact of apolipoprotein E genotypes on age at onset of symptoms and phenotypic expression in Wilson's disease. Brain 2000, 123: 585-590. First demonstration of an extragenic effect on the phenotypic expression of Wilson disease.
13. Nanji MS, Nguyen VT, Kawasoe JH, et al.: Haplotype and mutation analysis in Japanese patients with Wilson disease. Am J Hum Genet 1997, 60: 1423-1429.
14. Ferenci P, Caca K, Loudianos G, et al.: Diagnosis and phenotypic classification of Wilson disease. Liver Int 2003, 23: 139-142.
15. Shah AB, Chernov I, Zhang HT, et al.: Identification and analysis of mutations in the Wilson disease gene (ATP7B): Population frequencies, genotype-phenotype correlation, and functional analyses. Am J Hum Genet 1997, 61: 317-328.
16. Takeshita Y, Shimizu N, Yamaguchi Y, et al.: Two families with Wilson disease in which siblings showed different phenotypes. J Hum Genet 2002, 47: 543-547.
17. Schilsky ML, Scheinberg IH, Sternlieb I: Liver transplantation for Wilson's disease: Indications and outcome. Hepatology 1994, 19: 583-587.
18. Kasai N, Miyoshi I, Osanai T, et al.: Effects of sex hormones on fulminant hepatitis in LEC rats: A model of Wilson's disease. Lab Anim Sci 1992, 42: 363-368.
19. Du C, Fujii Y, Ito M, et al.: Dietary polyunsaturated fatty acids suppress acute hepatitis, alter gene expression and prolong survival of female Long-Evans Cinnamon rats, a model of Wilson disease. J Nutr Biochem 2004, 15: 273-280.
20. Muller T, van de Sluis B, Zhernakova A, et al.: The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis. J Hepatol 2003, 38: 164-168.
21. Stuehler B, Reichert J, Stremmel W, Schaefer M: Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients. J Mol Med 2004, 82: 629-634. These studies suggest that alterations in other proteins in the copper metabolic pathway may affect the phenotypic expression of Wilson disease. This concept is similar to that now being developed for iron overload disorders, where there are several different gene products that may act in concert to influence phenotypic expression of disease.
22. Yoshida Y, Tokusashi Y, Lee GH, Ogawa K: Intrahepatic transplantation of normal hepatocytes prevents Wilson's disease in Long-Evans cinnamon rats. Gastroenterology 1996, 111: 1654-1660. First study showing that successful transplantation of normal liver cells into LEC rats may prevent copper toxicosis.
23. Irani AN, Malhi H, Slehria S, et al.: Correction of liver disease following transplantation of normal rat hepatocytes into Long-Evans Cinnamon rats modeling Wilson's disease. Mol Ther 2001, 3: 302-309. Studies extending those by Yoshida et al. [22] demonstrating the need for at least 30% cell replacement to achieve prevention of copper toxicosis. Restoration of biliary copper excretion and holoceruloplasmin secretion were also demonstrated along with reduction in hepatic copper and prevention of cellular injury in rats successfully transplanted with normal rat hepatocytes.
24. Malhi H, Irani AN, Volenberg I, et al.: Early cell transplantation in LEC rats modeling Wilson's disease eliminates hepatic copper with reversal of liver disease. Gastroenterology 2002, 122: 438-447. The ability to transplant the normal liver cells into young LEC rats prevented the need for alkaloids and partial hepatectomy to achieve selective repopulation with transplanted cells.
25. Ha-Hao D, Merle U, Hofmann C, et al.: Chances and shortcomings of adenovirus-mediated ATP7B gene transfer in Wilson disease: Proof of principle demonstrated in a pilot study with LEC rats. Z Gastroenterol 2002, 40: 209-216.
26. Terada K, Nakako T, Yang XL, et al.: Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA. J Biol Chem 1998, 273: 1815-1820.
27. Terada K, Aiba N, Yang XL, et al.: Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B. FEBS Lett 1999, 448: 53-56.
28. Kren BT, Parashar B, Bandyopadhyay P, et al.: Correction of the UDP-glucuronosyltransferase gene defect in the gunn rat model of Crigler-Najjar syndrome type I with a chimeric oligonucleotide. Proc Natl Acad Sci U S A 1999, 31:96: 10349-10354.
29. Kren BT, Bandyopadhyay P, Steer CJ: In vivo site-directed mutagenesis of the factor IX gene by chimeric RNA/DNA oligonucleotides. Nat Med 1998, 4: 285-290.
30. Richa P, Thoma C, Kren BT, Steer CJ: Strategies for hepatic gene correction. J Drug Target 2002, 10: 133-141.