hepatolenticular degeneration

Summary

Summary: A rare autosomal recessive disease characterized by the deposition of copper in the BRAIN; LIVER; CORNEA; and other organs. It is caused by defects in the ATP7B gene encoding copper-transporting ATPase 2 (EC 3.6.3.4), also known as the Wilson disease protein. The overload of copper inevitably leads to progressive liver and neurological dysfunction such as LIVER CIRRHOSIS; TREMOR; ATAXIA and intellectual deterioration. Hepatic dysfunction may precede neurologic dysfunction by several years.

Top Publications

  1. doi Diagnosis and treatment of Wilson disease: an update
    Eve A Roberts
    Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
    Hepatology 47:2089-111. 2008
  2. ncbi The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene
    P C Bull
    Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
    Nat Genet 5:327-37. 1993
  3. ncbi Diagnosis and phenotypic classification of Wilson disease
    Peter Ferenci
    University of Vienna, Austria
    Liver Int 23:139-42. 2003
  4. ncbi Wilson's disease
    Aftab Ala
    UCL Institute of Hepatology, Hampstead Campus, Division of Medicine, Royal Free and University College Medical School, University College London, London, UK
    Lancet 369:397-408. 2007
  5. ncbi Apolipoprotein E gene (APOE) genotype in Wilson's disease: impact on clinical presentation
    T Litwin
    Institute of Psychiatry and Neurology, Second Department of Neurology, Sobieskiego 9, 02 957 Warsaw, Poland
    Parkinsonism Relat Disord 18:367-9. 2012
  6. ncbi Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis
    Sharon La Fontaine
    Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, 221 Burwood Highway, Burwood, VIC 3125, Australia
    Arch Biochem Biophys 463:149-67. 2007
  7. ncbi The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene
    J Wu
    Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
    Nat Genet 7:541-5. 1994
  8. ncbi Defective cellular localization of mutant ATP7B in Wilson's disease patients and hepatoma cell lines
    Dominik Huster
    Department of Internal Medicine II, University of Leipzig, Germany
    Gastroenterology 124:335-45. 2003
  9. ncbi Intracellular targeting of copper-transporting ATPase ATP7A in a normal and Atp7b-/- kidney
    Rachel Linz
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97239, USA
    Am J Physiol Renal Physiol 294:F53-61. 2008
  10. ncbi Recognition, diagnosis, and management of Wilson's disease
    G J Brewer
    Department of Human Genetics, University of Michigan, Ann Arbor, 48109 0618, USA
    Proc Soc Exp Biol Med 223:39-46. 2000

Detail Information

Publications260 found, 100 shown here

  1. doi Diagnosis and treatment of Wilson disease: an update
    Eve A Roberts
    Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
    Hepatology 47:2089-111. 2008
  2. ncbi The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene
    P C Bull
    Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
    Nat Genet 5:327-37. 1993
    ..Two WD patients were found to be homozygous for a seven base deletion within the coding region of Wc1. Wc1 is proposed as the gene for WD...
  3. ncbi Diagnosis and phenotypic classification of Wilson disease
    Peter Ferenci
    University of Vienna, Austria
    Liver Int 23:139-42. 2003
    ..After the meeting, a preliminary draft of a consensus report was mailed to all active participants and their comments were incorporated in the final text...
  4. ncbi Wilson's disease
    Aftab Ala
    UCL Institute of Hepatology, Hampstead Campus, Division of Medicine, Royal Free and University College Medical School, University College London, London, UK
    Lancet 369:397-408. 2007
    Progressive hepatolenticular degeneration, or Wilson's disease, is a genetic disorder of copper metabolism...
  5. ncbi Apolipoprotein E gene (APOE) genotype in Wilson's disease: impact on clinical presentation
    T Litwin
    Institute of Psychiatry and Neurology, Second Department of Neurology, Sobieskiego 9, 02 957 Warsaw, Poland
    Parkinsonism Relat Disord 18:367-9. 2012
    ..This study aimed to evaluate the impact of APOE genotype on the variability of WD phenotypic expression...
  6. ncbi Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis
    Sharon La Fontaine
    Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, 221 Burwood Highway, Burwood, VIC 3125, Australia
    Arch Biochem Biophys 463:149-67. 2007
    ....
  7. ncbi The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene
    J Wu
    Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
    Nat Genet 7:541-5. 1994
    ..This model will be important for studying liver pathophysiology, for developing therapy for Wilson disease and for studying the pathway of copper transport and its possible interaction with other heavy metals...
  8. ncbi Defective cellular localization of mutant ATP7B in Wilson's disease patients and hepatoma cell lines
    Dominik Huster
    Department of Internal Medicine II, University of Leipzig, Germany
    Gastroenterology 124:335-45. 2003
    ..Therefore, we characterized the subcellular localization of normal and mutant ATP7B in human livers and in hepatoma cell lines...
  9. ncbi Intracellular targeting of copper-transporting ATPase ATP7A in a normal and Atp7b-/- kidney
    Rachel Linz
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97239, USA
    Am J Physiol Renal Physiol 294:F53-61. 2008
    ..Our results suggest that both Cu-ATPases regulate renal copper, with ATP7A playing a major role in exporting copper via basolateral membranes and protecting renal tissue against copper overload...
  10. ncbi Recognition, diagnosis, and management of Wilson's disease
    G J Brewer
    Department of Human Genetics, University of Michigan, Ann Arbor, 48109 0618, USA
    Proc Soc Exp Biol Med 223:39-46. 2000
    ..Anticopper treatments have evolved considerably since the days when the only drug available was penicillamine. Zinc is now the recommended therapy for long-term management of the disease...
  11. ncbi Clinical molecular diagnosis of Wilson disease
    James Bennett
    Department of Medicine, University of Washington School of Medicine, Seattle Children s Hospital, Seattle, Washington 98105, USA
    Semin Liver Dis 31:233-8. 2011
    ..In this article, the authors review the sensitivity, limitations, and pitfalls of ATP7B sequencing in the diagnosis of Wilson disease. ATP7B sequencing should be standard practice in the diagnosis of Wilson disease...
  12. ncbi Genetic variability in the methylenetetrahydrofolate reductase gene (MTHFR) affects clinical expression of Wilson's disease
    Grazyna Gromadzka
    Institute of Psychiatry and Neurology, Second Department of Neurology, Warsaw, Poland
    J Hepatol 55:913-9. 2011
    ..The reason for the high variability in phenotypic expressions of WND is unknown. Hepatotoxic and neurotoxic effects of homocysteine (Hcy), as well as interrelationships between Hcy and Cu toxicity, were documented...
  13. ncbi Identification of high-copper-responsive target pathways in Atp7b knockout mouse liver by GSEA on microarray data sets
    Kan He
    School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, Peoples Republic of China
    Mamm Genome 22:703-13. 2011
    ..The results of our study may help us better understand the molecular mechanisms of high-copper effects in mice liver in genome-wide...
  14. ncbi Systematic review: clinical efficacy of chelator agents and zinc in the initial treatment of Wilson disease
    M Wiggelinkhuizen
    Department of Paediatric Gastroenterology, University Medical Centre Utrecht, Utrecht, The Netherlands
    Aliment Pharmacol Ther 29:947-58. 2009
    ..No consensus is available on the optimal initial treatment in Wilson disease...
  15. ncbi Analysis of renal impairment in children with Wilson's disease
    Xiao Hui Zhuang
    Department of Pediatrics, First Affiliated Hospital of Sun Yat sen University, Guangzhou 510080, China
    World J Pediatr 4:102-5. 2008
    ..This study was undertaken to find the clinical features of renal impairment in children with Wilson's disease or hepatolenticular degeneration (HLD).
  16. ncbi Neurologic Wilson's disease
    Matthew T Lorincz
    Department of Neurology, University of Michigan Health Systems, Ann Arbor, Michigan, USA
    Ann N Y Acad Sci 1184:173-87. 2010
    ..This review focuses on the neurologic features of Wilson's disease, its diagnosis, and treatment options...
  17. ncbi Copper-dependent trafficking of Wilson disease mutant ATP7B proteins
    J R Forbes
    Department of Medical Genetics, University of Alberta, Edmonton, Canada
    Hum Mol Genet 9:1927-35. 2000
    ..Our data have direct implications for WND diagnosis, indicating that decreased serum ceruloplasmin concentration is not likely to be observed with certain genetic variants of WND...
  18. ncbi Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation
    O I Buiakova
    Department of Genetics and Development, Columbia University, The NationalCenter for the Studyof Wilson s Disease and St Luke s Roosevelt Ho spital, New York, NY 10032, USA
    Hum Mol Genet 8:1665-71. 1999
    ..In summary, inactivation of the murine ATP7B gene produces a form of cirrhotic liver disease that resembles Wilson disease in humans and the 'toxic milk' phenotype in the mouse...
  19. ncbi Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease
    G Gromadzka
    Institute of Psychiatry and Neurology, Second Department of Neurology, Warsaw, Poland
    Clin Genet 68:524-32. 2005
    ..The effect of SMs on the WD phenotype was dose-dependent. It is concluded that mutations within ATP7B are very heterogeneous. Frameshift and nonsense mutations are associated with a severe phenotype of WD...
  20. ncbi Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin
    Peter V E van den Berghe
    Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, and the Netherlands Metabolomics Center, Utrecht, The Netherlands
    Hepatology 50:1783-95. 2009
    ..Treatment with pharmacological chaperones 4-phenylbutyrate (4-PBA) and curcumin, a clinically approved compound, partially restored protein expression of most ATP7B mutants...
  21. ncbi Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease
    George J Brewer
    Department of Human Genetics, University of Michigan Medical School, 5024 Kresge Bldg II, Ann Arbor, MI 48109 0534, USA
    Arch Neurol 63:521-7. 2006
    ..To compare tetrathiomolybdate and trientine in treating patients with the neurologic presentation of Wilson disease for the frequency of neurologic worsening, adverse effects, and degree of neurologic recovery...
  22. pmc Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes
    P De Bie
    Laboratory of Metabolic and Endocrine Diseases, Room KC 02 069 1, Lundlaan 6, 3584 EA Utrecht, The Netherlands
    J Med Genet 44:673-88. 2007
    ..As both disorders are characterised by an extensive clinical heterogeneity, we will discus how the underlying genetic defects correlate with the molecular functions of ATP7A and ATP7B and with the clinical expression of these disorders...
  23. ncbi Neurological manifestations in Wilson's disease: Report of 119 cases
    Alexandre Machado
    Department of Neurology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
    Mov Disord 21:2192-6. 2006
    ..Less frequent manifestations were chorea (16%) and athetosis (14%). Rare neurological presentations were seizures (4.2%), and pyramidal signs (3%)...
  24. ncbi Wilson disease
    Jonathan D Gitlin
    Edward Mallincroft Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Gastroenterology 125:1868-77. 2003
  25. ncbi p.H1069Q mutation in ATP7B and biochemical parameters of copper metabolism and clinical manifestation of Wilson's disease
    Graznya Gromadzka
    Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
    Mov Disord 21:245-8. 2006
    ..In compound heterozygotes, the phenotype of WD to a small extent depends on the type of mutation coexisting with the p.H1069Q. Besides genotype, additional modifying factors seem to determine WD manifestations...
  26. ncbi The molecular basis of copper-transport diseases
    J F Mercer
    Centre of Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, 221 Burwood Highway, VIC 3125, Burwood, Australia
    Trends Mol Med 7:64-9. 2001
    ....
  27. ncbi The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysis
    Janneke M Stapelbroek
    Department of Pediatric Gastroenterology, Wilhelmina Children s Hospital, University Medical Center, P O Box 85090, 3508 AB Utrecht, The Netherlands
    J Hepatol 41:758-63. 2004
    ..We examined whether H1069Q, the most common ATP7B mutation, is associated with a specific phenotype...
  28. ncbi Genotype-phenotype correlation in Italian children with Wilson's disease
    Emanuele Nicastro
    Department of Pediatrics, University of Naples Federico II, Naples, Italy
    J Hepatol 50:555-61. 2009
    ..Wilson's disease phenotype is very variable for clinical and laboratory features. Our aim was to assess the role of the type of ATP7B disease causing mutations on Wilson's disease phenotype...
  29. ncbi Wilson's disease tremor is associated with magnetic resonance imaging lesions in basal ganglia structures
    Martin Südmeyer
    Department of Neurology, Heinrich Heine University, Dusseldorf, Germany
    Mov Disord 21:2134-9. 2006
    ..Our results demonstrate for the first time that Wilson's disease tremor is associated with lesions of the globus pallidus, the head of the caudate nucleus, and the substantia nigra...
  30. ncbi Genetic testing for Wilson disease: availability and utility
    Michael L Schilsky
    Departments of Medicine and Surgery, Division of Digestive Diseases and Transplant and Immunology, Yale University School of Medicine, New Haven, CT 06520, USA
    Curr Gastroenterol Rep 12:57-61. 2010
    ..This test eventually will be incorporated into the diagnostic armamentarium, allowing timely diagnosis and perhaps reversal or even prevention of further copper-induced injury...
  31. pmc Urinary copper elevation in a mouse model of Wilson's disease is a regulated process to specifically decrease the hepatic copper load
    Lawrence W Gray
    Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA
    PLoS ONE 7:e38327. 2012
    ..These results demonstrate that the body regulates copper export through more than one mechanism; better understanding of urinary copper excretion may contribute to an improved diagnosis and monitoring of WD...
  32. ncbi Ferrous and ferric iron accumulates in the brain of aged Long-Evans Cinnamon rats, an animal model of Wilson's disease
    Jong Min Kim
    Department of Neurology, Seoul National University, Bundang Hospital, South Korea
    Neurosci Lett 382:143-7. 2005
    ..Further studies are required to elucidate the mechanisms of Cu and iron accumulations and of their effects...
  33. ncbi Influence of homozygosity for methionine at codon 129 of the human prion gene on the onset of neurological and hepatic symptoms in Wilson disease
    Uta Merle
    Department of Gastroenterology and Hepatology, University Hospital, Heidelberg, Germany
    Arch Neurol 63:982-5. 2006
    ..The prion-related protein (PrP) has been shown to bind copper in vitro and might therefore influence Wilson disease...
  34. ncbi Pathology of the liver in copper overload
    Melanie Johncilla
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
    Semin Liver Dis 31:239-44. 2011
    ..Copper and copper-associated protein accumulation may also be seen in chronic biliary obstructive processes...
  35. ncbi Gender differences in Wilson's disease
    T Litwin
    2nd Department of Neurology, Institute Psychiatry and Neurology, Warsaw, Poland
    J Neurol Sci 312:31-5. 2012
    ..Wilson's disease (WD) is an inherited disorder of copper metabolism. Although well documented in many disorders, gender hasn't been directly addressed in WD; therefore, our aim was to evaluate gender differences in WD...
  36. ncbi Neuroinflammatory and behavioural changes in the Atp7B mutant mouse model of Wilson's disease
    Dick Terwel
    Department of Neurology, Clinical Neurosciences, Bonn University, Bonn, Germany
    J Neurochem 118:105-12. 2011
    ..These mice can be used to evaluate therapeutic strategies to alleviate behavioural disturbances and cerebral pathology observed in WD...
  37. ncbi Evolving perspectives in Wilson disease: diagnosis, treatment and monitoring
    Karl Heinz Weiss
    University Hospital Heidelberg, Internal Medicine IV, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
    Curr Gastroenterol Rep 14:1-7. 2012
    ..In this article, we review current diagnostic and therapeutic approaches in WD...
  38. ncbi Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease
    Slavka Vrabelova
    Center of Molecular Biology and Gene Therapy, University Hospital Brno, Cernopolni 9, 625 00 Brno, Czech Republic
    Mol Genet Metab 86:277-85. 2005
    ..Screening of five prevalent mutations is predicted to reveal 70% of all mutant alleles presented in WD patients. This will provide a good starting point for early clinical classification of WD in our population...
  39. ncbi The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene
    N Sasaki
    RIKEN Tsukuba Life Science Center, Institute of Physical and Chemical Research, Ibaraki, Japan
    Biochem Biophys Res Commun 202:512-8. 1994
    ..This rat WD gene was mapped to 16q12.23-12.3 by fluorescence in situ hybridization and mouse x rat somatic cell hybrid analysis...
  40. ncbi Oxidative stress and pro-apoptotic conditions in a rodent model of Wilson's disease
    Alberta Samuele
    Laboratory of Functional Neurochemistry, Neurological Institute C Mondino, Via Mondino, 2 27100 Pavia, Italy
    Biochim Biophys Acta 1741:325-30. 2005
    ..Hence, we assume that enhanced oxidative stress may play a central role in the cell degeneration in WD, at the main sites of copper deposition, with discrete pro-apoptotic conditions developing in distal areas...
  41. ncbi Treatment of Wilson's disease with zinc XVI: treatment during the pediatric years
    G J Brewer
    University of Michigan Medical School, the departments of Human Genetics, Ann Arbor, MI 48109-0618, USA
    J Lab Clin Med 137:191-8. 2001
    ..Our data are strongest in children above 10 years of age. More work needs to be done in very young children, and the cholesterol observations need to be studied further...
  42. ncbi Pathology, clinical features and treatments of congenital copper metabolic disorders--focus on neurologic aspects
    Hiroko Kodama
    Department of Pediatrics, Teikyo University School of Medicine, Tokyo, Japan
    Brain Dev 33:243-51. 2011
    ..Neurologic worsening in patients treated with tetrathiomolybdate has been reported to be lower than rates of neurologic worsening when treating with other chelating agents...
  43. ncbi The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis
    Thomas Muller
    Department of Pediatrics, University of Innsbruck, Innsbruck, Austria
    J Hepatol 38:164-8. 2003
    ..We recently cloned the gene causing copper toxicosis in Bedlington terriers, MURR1, as well as the orthologous human gene on chromosome 2p13-p16...
  44. ncbi Evidence for a critical role of ceruloplasmin oxidase activity in iron metabolism of Wilson disease gene knockout mice
    Uta Merle
    Department of Gastroenterology, University Hospital, Heidelberg, Germany
    J Gastroenterol Hepatol 25:1144-50. 2010
    ..Therefore, the present study was carried out to elucidate iron metabolism in Atp7b(-/-) mice, an animal model of Wilson disease...
  45. ncbi Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults
    Ronen Arnon
    Mount Sinai School of Medicine, Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029, USA
    Clin Transplant 25:E52-60. 2011
    ..Liver transplantation (LT) is lifesaving for patients with Wilson disease (WD) presenting with fulminant hepatic failure (FHF) or chronic liver disease (CLD) unresponsive to treatment...
  46. pmc Liver mitochondrial membrane crosslinking and destruction in a rat model of Wilson disease
    Hans Zischka
    Institute of Toxicology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
    J Clin Invest 121:1508-18. 2011
    ..Together, these findings suggest that the mitochondrion constitutes a pivotal target of copper in WD...
  47. pmc Systems biology approach to Wilson's disease
    Jason L Burkhead
    University of Alaska Anchorage, Anchorage, AK 99508, USA
    Biometals 24:455-66. 2011
    ..A systems biology approach promises to generate a comprehensive view of WD onset and progression, thus helping with a more fine-tune treatment and monitoring of the disorder...
  48. pmc Wilson disease at a single cell level: intracellular copper trafficking activates compartment-specific responses in hepatocytes
    Martina Ralle
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Biol Chem 285:30875-83. 2010
    ..These observations suggest new stage-specific as well as general biomarkers for WD. The model for the dynamic role of copper in WD is proposed...
  49. ncbi Neurologically presenting Wilson's disease: epidemiology, pathophysiology and treatment
    George J Brewer
    Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109 0534, USA
    CNS Drugs 19:185-92. 2005
    ..In the absence of availability of tetrathiomolybdate, zinc or trientine are the next best choices...
  50. ncbi Homozygous mutations in the conserved ATP hinge region of the Wilson disease gene: association with liver disease
    Kassem Barada
    Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
    J Clin Gastroenterol 44:432-9. 2010
    ..To determine whether any correlation exists between the phenotype and genotype of 2 Lebanese families with members affected with Wilson disease (WD)...
  51. ncbi High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model of Wilson disease
    Dominik Huster
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Biol Chem 282:8343-55. 2007
    ..The identification of the network of specific copper-responsive targets facilitates further mechanistic analysis of human disorders of copper misbalance...
  52. ncbi Treatment of Wilson's disease with tetrathiomolybdate: V. Control of free copper by tetrathiomolybdate and a comparison with trientine
    George J Brewer
    Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
    Transl Res 154:70-7. 2009
    ..Tetrathiomolybdate controlled copper less well in the dose regimen study (study 3) than in the previous 2 studies of tetrathiomolybdate treatment, probably because of a change in the way "away from food" tetrathiomolybdate was given...
  53. ncbi Wilson disease
    Mounif El-Youssef
    Division of Gastroenterology and Hepatology and Internal Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minn 55905, USA
    Mayo Clin Proc 78:1126-36. 2003
    ..The evolution of Wilson disease from a uniformly fatal disease to an eminently treatable disease during the past century is an example of the remarkable advances of modern medicine...
  54. ncbi Sequential MRI changes in Wilson's disease with de-coppering therapy: a study of 50 patients
    S Sinha
    Department of Neurology, National Institute of Mental Health and Neurosciences NIMHANS, Bangalore, India
    Br J Radiol 80:744-9. 2007
    ..Patients with extensive changes, white-matter involvement and severe diffuse atrophy had a poor prognosis In conclusion, the majority of patients with WD showed variable improvement in clinical and MRI features when treated...
  55. ncbi XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders
    Arjmand R Mufti
    Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA
    Mol Cell 21:775-85. 2006
    ..These data provide an unsuspected link between copper homeostasis and the regulation of cell death through XIAP and may contribute to the pathophysiology of copper toxicosis disorders...
  56. ncbi Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing
    Peter Ferenci
    Department of Internal Medicine IV, University of Vienna, Wahringer Gurtel 18 20, 1090, Vienna, Austria
    Hum Genet 120:151-9. 2006
    ..Knowledge of the differences in the worldwide distribution of particular mutations will help to design shortcuts for genetic diagnosis of WD...
  57. ncbi Wilson's disease in children: 37-year experience and revised King's score for liver transplantation
    Anil Dhawan
    Paediatric Liver Service, King s College Hospital, London, UK
    Liver Transpl 11:441-8. 2005
    ..In conclusion, the new Wilson Index is more sensitive and specific in predicting mortality without transplantation than the old scoring system, but needs to be validated in a larger number of patients...
  58. ncbi Chronological changes in tissue copper, zinc and iron in the toxic milk mouse and effects of copper loading
    Katrina J Allen
    Liver Research Group, Murdoch Childrens Research Institute, Royal Children s Hospital, Parkville, Victoria, 3052, Australia
    Biometals 19:555-64. 2006
    ..The livers of copper-loaded tx mice had a lower zinc concentration than control tx mice, whilst the kidney had double the concentration of iron suggesting that there was increased erythrocyte hemolysis in the copper-loaded mutants...
  59. ncbi Wilson's disease: cranial MRI observations and clinical correlation
    S Sinha
    Department of Neurology, National Institute of Mental Health and Neurosciences NIMHANS, Bangalore, India
    Neuroradiology 48:613-21. 2006
    ..Study of MRI changes may be useful in diagnosis, prognosis and better understanding of the pathophysiology of Wilson's disease (WD). We aimed to describe and correlate the MRI abnormalities of the brain with clinical features in WD...
  60. ncbi Sequence variation database for the Wilson disease copper transporter, ATP7B
    Susan M Kenney
    Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada
    Hum Mutat 28:1171-7. 2007
    ..The tables in this database are a valuable resource for the study of population variation and the function of the transporter, and will assist in the identification of disease and non-disease-causing sequence variants...
  61. ncbi Wilson disease in septuagenarian siblings: Raising the bar for diagnosis
    Aftab Ala
    Division of Liver Diseases, Recanati Miller Transplant Institute, The Mount Sinai Medical Center, New York, NY, USA
    Hepatology 41:668-70. 2005
    ..Environmental and extragenic factors are pivotal determinants of disease phenotype. We suggest that WD must be considered at all ages in patients with hepatic disease, neurological disease, or psychiatric symptoms...
  62. ncbi Mapping, cloning and genetic characterization of the region containing the Wilson disease gene
    K Petrukhin
    Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York 10032
    Nat Genet 5:338-43. 1993
    ..Our haplotype and mutation analyses predict that approximately half of all WD mutations will be rare in the American and Russian populations...
  63. pmc Haplotypes and mutations in Wilson disease
    G R Thomas
    Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
    Am J Hum Genet 56:1315-9. 1995
    ..The use of the haplotypes that we have identified provides an important guide for the identification of known mutations and can facilitate future mutation searches...
  64. ncbi Wilson disease
    Dominik Huster
    Department of Gastroenterology and Oncology, Deaconess Hospital Leipzig, Georg Schwarz Str 49, 04177 Leipzig, Germany
    Best Pract Res Clin Gastroenterol 24:531-9. 2010
    ....
  65. ncbi Wilson's Disease
    Ronald F Pfeiffer
    Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    Semin Neurol 27:123-32. 2007
    ..This article discusses the epidemiology, genetics, pathophysiology, clinical features, diagnostic testing, and treatment of Wilson's disease...
  66. ncbi Wilson disease: novel mutations in the ATP7B gene and clinical correlation in Brazilian patients
    Marta M Deguti
    Department of Gastroenterology, Sao Paulo University School of Medicine, Sao Paulo, Brazil
    Hum Mutat 23:398. 2004
    ..Exons 8 and 15 should be preferentially screened in WD cases from Brazil. Phenotype variation among subjects with the same ATP7B genotype suggests that modifying factors play an additional role in the pathogenesis of WD...
  67. pmc Distinct Wilson's disease mutations in ATP7B are associated with enhanced binding to COMMD1 and reduced stability of ATP7B
    Prim de Bie
    Laboratory of Metabolic and Endocrine Diseases, Division of Biomedical Genetics, Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands
    Gastroenterology 133:1316-26. 2007
    ..ATP7B interacts with COMMD1, a protein that is deleted in Bedlington terriers with hereditary copper toxicosis. Here we characterized the implications of the interaction between COMMD1 and ATP7B in relation to the pathogenesis of WD...
  68. ncbi The Wilson disease gene: spectrum of mutations and their consequences
    G R Thomas
    Research Institute, Hospital for Sick Children, Toronto, Canada
    Nat Genet 9:210-7. 1995
    ..The mutations identified provide an explanation for at least part of the wide phenotypic variation observed in Wilson disease...
  69. ncbi Late-onset Wilson's disease
    Peter Ferenci
    Department of Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
    Gastroenterology 132:1294-8. 2007
    ..The clinical symptoms and age at onset of Wilson's disease (WD) are highly variable. This study investigated patients who became symptomatic at >40 years of age...
  70. ncbi Structure of the ATP binding domain from the Archaeoglobus fulgidus Cu+-ATPase
    Matthew H Sazinsky
    Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA
    J Biol Chem 281:11161-6. 2006
    ..Finally, the CopA ATPBD structure provides a basis for understanding the likely structural and functional effects of various mutations that lead to Wilson and Menkes diseases...
  71. pmc Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study
    U Merle
    Department of Gastroenterology, University Hospital Heidelberg, Neuenheimer Feld 410, Heidelberg 69120, Germany
    Gut 56:115-20. 2007
    ..Wilson's disease is a rare inborn disease related to copper storage, leading to liver cirrhosis and neuropsychological deterioration. Clinical data on larger cohorts are limited owing to low disease frequency...
  72. ncbi The Jackson toxic milk mouse as a model for copper loading
    V Coronado
    Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7
    Mamm Genome 12:793-5. 2001
  73. ncbi Copper storage diseases: Menkes, Wilsons, and cancer
    Kenyon G Daniel
    The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan, USA
    Front Biosci 9:2652-62. 2004
    ..Wilsons and Menkes diseases are two such cases. Wilsons disease (hepatolenticular degeneration) is an autosomal recessive disorder resulting in extreme accumulation of copper in the liver with ..
  74. ncbi Mutation analysis of Wilson disease in the Spanish population -- identification of a prevalent substitution and eight novel mutations in the ATP7B gene
    E Margarit
    Department of Genetics, Hospital Clinic, Barcelona, Spain
    Clin Genet 68:61-8. 2005
    ..Molecular diagnosis of WD is very useful in clinical practice to confirm or support clinical suspicion...
  75. ncbi Liver transplantation for Wilson's disease: The burden of neurological and psychiatric disorders
    Valentina Medici
    Department of Surgical and Gastroenterological Sciences, Gastroenterology and Liver Transplant Sections, University of Padua, Padua, Italy
    Liver Transpl 11:1056-63. 2005
    ..In conclusion, a combination of hepatic and neuropsychiatric conditions deserves careful neurological evaluation, which should contraindicate OLT in case of severe neurological impairment...
  76. ncbi MR imaging of the brain in patients with hepatic form of Wilson's disease
    D Kozic
    Diagnostic Imaging Center, Institute of Oncology, Sremska Kamenica, Belgrade, Yugoslavia
    Eur J Neurol 10:587-92. 2003
    ..The lower frequency of lesions in the group of treated in comparison with untreated patients indicated that they might be reversible in the course of chronic chelating therapy...
  77. ncbi Mitochondrial structure and function in the untreated Jackson toxic milk (tx-j) mouse, a model for Wilson disease
    Eve A Roberts
    Genetics and Genomic Biology Program, Hospital for Sick Children Research Institute, University of Toronto, 555 University Avenue, Toronto, Ontario, Canada
    Mol Genet Metab 93:54-65. 2008
    ..Levels of two mitochondrial antioxidant proteins capable of binding copper, thioredoxin-2 and peroxiredoxin-3, rose over the first 6 months of life. Mitochondrial changes occur early in WD and reflect complex, probably oxidative, injury...
  78. ncbi Wilson disease: current status and the future
    Michael L Schilsky
    Division of Digestive Diseases, Adult Liver Transplant, Yale University Medical Center, New Haven, CT 06520, USA
    Biochimie 91:1278-81. 2009
    ..Future therapies may include hepatocyte transplantation and gene therapy, both of which have been tested and shown to work in animal models of Wilson disease. Future human studies await advances in these areas...
  79. ncbi Diagnosis of Wilson's disease: a comprehensive review
    Chloe M Mak
    Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
    Crit Rev Clin Lab Sci 45:263-90. 2008
    ..Ceruloplasmin oxidase activity and serum free-copper concentration should be monitored in patients on long-term de-coppering therapy to prevent iatrogenic copper deficiency...
  80. ncbi Wilson's disease: an update
    Shyamal K Das
    Movement Disorders Clinic, Bangur Institute of Neurology, Kolkata, India
    Nat Clin Pract Neurol 2:482-93. 2006
    ....
  81. ncbi IQGAP1 and vimentin are key regulator genes in naturally occurring hepatotumorigenesis induced by oxidative stress
    Akihito Tsubota
    Institute of Clinical Medicine and Research, Jikei University School of Medicine, 163 1 Kashiwa shita, Kashiwa, Chiba 277 8567, Japan
    Carcinogenesis 31:504-11. 2010
    ..These findings enhance our understanding of the multistep hepatotumorigenesis and identification of target molecules for novel treatments...
  82. ncbi Wilson disease
    Cord Langner
    Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria
    Virchows Arch 445:111-8. 2004
    ..Although the value of molecular genetic testing is limited due to the high number of possible gene mutations, polymerase chain reaction may be useful for the evaluation of family members of homozygous index patients...
  83. ncbi The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease
    Mario Lovicu
    Institute of Neurogenetics and Neuropharmacology, CNR Cagliari, Cagliari, Italy
    J Gastroenterol 41:582-7. 2006
    ..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...
  84. ncbi High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype-genotype analysis
    K Caca
    Department of Medicine II, University of Leipzig, Philipp Rosenthal Strasse 27, 04103 Leipzig, Germany
    J Hepatol 35:575-81. 2001
    ..Wilson disease is caused by a large number of different mutations in the ATP7B gene. Wilson disease patients from a homogeneous ethnical background (Saxonia) were studied for distribution and phenotypes of ATP7B mutations...
  85. ncbi Pathophysiology and clinical features of Wilson disease
    Peter Ferenci
    Department of Internal Medicine IV, Gastroenterology and Hepatology, Medical University of Vienna, Wahringer Gurtel 18 20, A 1090 Vienna, Austria
    Metab Brain Dis 19:229-39. 2004
    ..Initial treatment for symptomatic patients should include a chelating agent (penicillamine or trientine). Treatment of presymptomatic patients or maintenance therapy can also be accomplished with zinc...
  86. ncbi COMMD1 (MURR1) as a candidate in patients with copper storage disease of undefined etiology
    V A Coronado
    Clin Genet 68:548-51. 2005
  87. pmc Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation, and functional analyses
    A B Shah
    Department of Genetics and Development, Columbia University, New York, NY 10032, USA
    Am J Hum Genet 61:317-28. 1997
    ..Finally, lymphoblast cell lines from individuals homozygous for His1069Glu and 4 other mutations all demonstrated significantly decreased copper-stimulated ATPase activity...
  88. pmc Liver biopsy in modern clinical practice: a pediatric point-of-view
    Nadia Ovchinsky
    Department of Pediatrics, Morgan Stanley Children s Hospital of New York, NY, USA
    Adv Anat Pathol 19:250-62. 2012
    ..This review presents specific indications, considerations, methods, complications, contraindications, and alternatives for pediatric liver biopsy...
  89. ncbi Extensive cortico-subcortical lesions in Wilson's disease: clinico-pathological study of two cases
    Jacqueline Mikol
    Department of Pathology, Denis Diderot University, Paris, France
    Acta Neuropathol 110:451-8. 2005
    ..Cerebral copper content in white matter and putamen of case 1 was at the same level as in common WD but accumulation of unbound copper in the white matter was a distinctive feature, which suggested a pathological neurotoxic effect...
  90. ncbi Prion protein gene codon 129 modulates clinical course of neurological Wilson disease
    Stephanie Grubenbecher
    Institute for Neuropathology, Heinrich Heine University of Dusseldorf, Dusseldorf, Germany
    Neuroreport 17:549-52. 2006
    ..PRNP 129 methionine homozygosity, however, led to significantly more severe neurological symptoms in elderly patients, particularly tremor, supporting the notion that PRNP 129 homozygosity contributes to neuronal vulnerability...
  91. ncbi Histological changes in monoaminergic neurons of Long-Evans Cinnamon rats
    H Kawano
    Department of Pediatrics, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamikyo ku, Kyoto 602 8566, Japan
    Brain Res 915:25-31. 2001
    ..These results suggest that age-dependent changes in copper concentrations of Long-Evans Cinnamon rats were related to changes in monoaminergic neuron systems...
  92. ncbi Genetic modifiers of liver injury in hereditary liver disease
    Aftab Ala
    Centre for Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Frimley Park Hospital NHS Foundation Trust, Surrey, United Kingdom
    Semin Liver Dis 31:208-14. 2011
    ..Homozygosity for the A1-ATZ mutation is generally required for the development of liver disease in A1-AT although there is increasing evidence for modifier effects from a heterozygous genotype in other liver diseases...
  93. ncbi Wilson disease in children: analysis of 57 cases
    Nina Manolaki
    First Department of Pediatrics, Athens University, Aghia Sophia Children s Hospital, Athens, Greece
    J Pediatr Gastroenterol Nutr 48:72-7. 2009
    ..Affected children may be entirely asymptomatic and the diagnosis problematic. Herein we present the clinical and laboratory characteristics of 57 children with WD and point out the diagnostic difficulties in a pediatric population...
  94. pmc Difference in stability of the N-domain underlies distinct intracellular properties of the E1064A and H1069Q mutants of copper-transporting ATPase ATP7B
    Oleg Y Dmitriev
    Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
    J Biol Chem 286:16355-62. 2011
    ..We conclude that the structural stability of the N-domain rather than the loss of ATP binding plays a defining role in the ability of ATP7B to reach the trans-Golgi network, thus contributing to phenotypic variability in WD...
  95. ncbi Wilson disease: description of 282 patients evaluated over 3 decades
    Arun B Taly
    Department of Neurology, National Institute of Mental Health and Neurosciences NIMHANS, Bangalore, Karnataka, India
    Medicine (Baltimore) 86:112-21. 2007
    ..To conclude, despite increased awareness and recognition and significant inroads into therapeutic frontiers, follow-up remains poor in developing countries and a return to previous level of functioning is not universal...
  96. ncbi Wilson's disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI
    Maria do Desterro Leiros da Costa
    Movement Disorders Unit, Federal University of Paraiba, Paraiba, Brazil
    Neuroradiology 51:627-33. 2009
    ..Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce...
  97. ncbi The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene
    R E Tanzi
    Neurology Department, Harvard Medical School, Boston, Massachusetts 02114
    Nat Genet 5:344-50. 1993
    ....
  98. ncbi Evaluation of the scoring system for the diagnosis of Wilson's disease in children
    Samita Koppikar
    Liver Int 25:680-1. 2005
  99. ncbi Different neurological outcome of liver transplantation for Wilson's disease in two homozygotic twins
    Marco Senzolo
    Gastroenterology, Department of Surgical and Gastroenterological Sciences, University of Padua, Padua, Italy
    Clin Neurol Neurosurg 109:71-5. 2007
    ..The presence of neurological clinical manifestations in Wilson's disease should recommend caution indicating liver transplantation, because irreversible brain damage may exist...
  100. ncbi Mass screening for Wilson's disease: results and recommendations
    Y Yamaguchi
    Second Department of Pediatrics, Toho University School of Medicine, Ohashi Hospital, Tokyo, Japan
    Pediatr Int 41:405-8. 1999
    ..The age of 3 years is thought to be the best point for Wilson's disease mass screening. In this paper, a review of mass screening for Wilson's disease in Japan using a specific monoclonal antibody to holoceruloplasmin is presented...
  101. ncbi Usefulness of penicillamine-stimulated urinary copper excretion in the diagnosis of adult Wilson's disease
    José Ramón Foruny
    Department of Gastroenterology, Hospital Ramon y Cajal, Madrid, Spain
    Scand J Gastroenterol 43:597-603. 2008
    ..The aim of this study was to determine the usefulness of penicillamine-stimulated urinary copper excretion (PS-UCE), a non-invasive diagnostic test, for the diagnosis of WD in adults...

Research Grants15

  1. PHASE III TRIAL OF TETRATHIOMOLYBDATE IN PRIMARY BILIAR*
    George Brewer; Fiscal Year: 2007
    ..Abstract Not Provided ..
  2. Characterization of nuclear proteome in normal and diseased liver
    Svetlana Lutsenko; Fiscal Year: 2007
    ..The proteomic information and methodology generated during this study will be applicable for analysis of other hepatic disorders in humans. [unreadable] [unreadable] [unreadable]..
  3. Strategies for mapping origins in mammalian genomes
    JOYCE HAMLIN; Fiscal Year: 2009
    ..By comparing these data to the distributions identified in Aim 1. we will define aspects of chromatin architecture that characterize active origins, origin clusters, and/or local genes. ..
  4. Copper Transport in Lactation
    Maria Linder; Fiscal Year: 2009
    ....
  5. Type-1 Diabetes: Zn2+ Potentiated Beta-Cell Death By Sirtuin-Mediated NAD+ Loss
    CHRISTIAN THOMAS SHELINE; Fiscal Year: 2010
    ..These experiments will test novel therapeutic compounds (pyruvate, sirtinol) and mechanisms (NAD+loss, sirtuins) involved in Zn2+ mediation of beta-cell death in type-1 diabetes. ..
  6. INFLAMMATATION, IRON AND FERRITINS IN IRON ABSORPTION
    Maria Linder; Fiscal Year: 2001
    ..This is important since very little is currently known about these process at the molecular level and aberrations result in chronic over-absorption and iron overload. This is an adaptive response which is poorly understood. ..
  7. AMPLIFICATION--MODEL FOR GENETIC INSTABILITY IN CANCER
    JOYCE HAMLIN; Fiscal Year: 2005
    ..abstract_text> ..
  8. BIOLOGICAL ROLES OF IRON IN HUMAN NUTRITION
    ZENA HARRIS; Fiscal Year: 2004
    ..4) To examine the role of the hemochromatosis gene (HFE) in cellular efflux by generating double knockouts in CP and HEF mice. ..
  9. Embryonic Stem Cell Model of Polyglutamine Disease
    MATTHEW LORINCZ; Fiscal Year: 2007
    ..Once the pathologic mechanisms of mutant huntingtin are understood it will become possible to design rational therapeutics. ..
  10. Copper Complexing with Tetrathiomolybdate in a Murine Model of Alzheimers Disease
    Joseph Quinn; Fiscal Year: 2007
    ..These are the critical pieces of information for determining if TM should be evaluated in clinical trials for either the prevention or the treatment of Alzheimer's disease. [unreadable] [unreadable] [unreadable]..
  11. ZINC NEUROTOXICITY
    Christian Sheline; Fiscal Year: 2004
    ....
  12. OBSESSIONS/COMPULSIONS IN HUNTINGTON'S DISEASE
    Karen Anderson; Fiscal Year: 2005
    ..The ultimate goal is to provide the candidate with the skill and knowledge base to become an independent, multidisciplinary investigator of neuropsychiatric illness. ..
  13. A MULTI-CENTER THERAPY TRIAL FOR ACUTE LIVER FAILURE
    William Lee; Fiscal Year: 2004
    ..The overall goal is to apply modern clinical, epidemiological and virological techniques to the study of this rare but devastating illness. ..