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Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes.
J Med Genet. 2007 Nov; 44(11):673-88.JM

Abstract

The trace metal copper is essential for a variety of biological processes, but extremely toxic when present in excessive amounts. Therefore, concentrations of this metal in the body are kept under tight control. Central regulators of cellular copper metabolism are the copper-transporting P-type ATPases ATP7A and ATP7B. Mutations in ATP7A or ATP7B disrupt the homeostatic copper balance, resulting in copper deficiency (Menkes disease) or copper overload (Wilson disease), respectively. ATP7A and ATP7B exert their functions in copper transport through a variety of interdependent mechanisms and regulatory events, including their catalytic ATPase activity, copper-induced trafficking, post-translational modifications and protein-protein interactions. This paper reviews the extensive efforts that have been undertaken over the past few years to dissect and characterise these mechanisms, and how these are affected in Menkes and Wilson disease. 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.

Authors+Show Affiliations

Laboratory of Metabolic and Endocrine Diseases, Room KC.02.069.1, Lundlaan 6, 3584 EA Utrecht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

17717039

Citation

de Bie, P, et al. "Molecular Pathogenesis of Wilson and Menkes Disease: Correlation of Mutations With Molecular Defects and Disease Phenotypes." Journal of Medical Genetics, vol. 44, no. 11, 2007, pp. 673-88.
de Bie P, Muller P, Wijmenga C, et al. Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. J Med Genet. 2007;44(11):673-88.
de Bie, P., Muller, P., Wijmenga, C., & Klomp, L. W. (2007). Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. Journal of Medical Genetics, 44(11), 673-88.
de Bie P, et al. Molecular Pathogenesis of Wilson and Menkes Disease: Correlation of Mutations With Molecular Defects and Disease Phenotypes. J Med Genet. 2007;44(11):673-88. PubMed PMID: 17717039.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. AU - de Bie,P, AU - Muller,P, AU - Wijmenga,C, AU - Klomp,L W J, Y1 - 2007/08/23/ PY - 2007/8/25/pubmed PY - 2007/12/6/medline PY - 2007/8/25/entrez SP - 673 EP - 88 JF - Journal of medical genetics JO - J. Med. Genet. VL - 44 IS - 11 N2 - The trace metal copper is essential for a variety of biological processes, but extremely toxic when present in excessive amounts. Therefore, concentrations of this metal in the body are kept under tight control. Central regulators of cellular copper metabolism are the copper-transporting P-type ATPases ATP7A and ATP7B. Mutations in ATP7A or ATP7B disrupt the homeostatic copper balance, resulting in copper deficiency (Menkes disease) or copper overload (Wilson disease), respectively. ATP7A and ATP7B exert their functions in copper transport through a variety of interdependent mechanisms and regulatory events, including their catalytic ATPase activity, copper-induced trafficking, post-translational modifications and protein-protein interactions. This paper reviews the extensive efforts that have been undertaken over the past few years to dissect and characterise these mechanisms, and how these are affected in Menkes and Wilson disease. 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. SN - 1468-6244 UR - https://www.unboundmedicine.com/medline/citation/17717039/Molecular_pathogenesis_of_Wilson_and_Menkes_disease:_correlation_of_mutations_with_molecular_defects_and_disease_phenotypes_ L2 - http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=17717039 DB - PRIME DP - Unbound Medicine ER -