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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Phillips, J. D. Articles by Kushner, J. P. Search for Related Content PubMed PubMed Citation Articles by Phillips, J. D. Articles by Kushner, J. P. Related Collections Red Cells Plenary Papers Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2001, Vol. 98, No. 12, pp. 3179-3185 PLENARY PAPER Functional consequences of naturally occurring mutations in human uroporphyrinogen decarboxylase John D. Phillips, Tiffany L. Parker, Heidi L. Schubert, Frank G. Whitby, Christopher P. Hill, and James P. Kushner From the Departments of Medicine and Biochemistry, University of Utah School of Medicine, Salt Lake City. Functional consequences of 12 mutations10 missense, 1 splicing defect, and 1 frameshift mutationwere characterized in the uroporphyrinogen decarboxylase (URO-D) gene found in Utah pedigrees with familial porphyria cutanea tarda (F-PCT). All but one mutation altered a restriction site in the URO-D gene, permitting identification of affected relatives using a combination of polymerase chain reaction and restriction enzyme digestion. In a bacterial expression system, 3 of the missense mutants were found in inclusion bodies, but 7 were expressed as soluble proteins. Enzymatic activity of soluble, recombinant mutant URO-D genes ranged from 29% to 94% of normal. URO-D mRNA levels in Epstein-Barr-virus transformed cells derived from patients were normal (with the exception of the frameshift mutation) even though protein levels were lower than normal, suggesting that missense mutations generally cause unstable URO-Ds in vivo. The crystal structures of 3 mutant URO-Ds were solved, and the structural consequences of the mutations were defined. All missense mutations reported here and by others were mapped to the crystal structure of URO-D, and structural effects were predicted. These studies define structural and functional consequences of URO-D mutations occurring in patients with F-PCT. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. K. Aarsand, H. Boman, and S. Sandberg Familial and Sporadic Porphyria Cutanea Tarda: Characterization and Diagnostic Strategies Clin. Chem., April 1, 2009; 55(4): 795 - 803. [Abstract] [Full Text] [PDF] R. S. Ajioka, J. D. Phillips, R. B. Weiss, D. M. Dunn, M. W. Smit, S. C. Proll, M. G. Katze, and J. P. Kushner Down-regulation of hepcidin in porphyria cutanea tarda Blood, December 1, 2008; 112(12): 4723 - 4728. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020