These authors contributed equally to this work.
Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives
Article first published online: 17 MAR 2009
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard
Volume 75, Issue 4, pages 346–353, April 2009
How to Cite
Badenas, C., To-Figueras, J., Phillips, J., Warby, C., Muñoz, C. and Herrero, C. (2009), Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives. Clinical Genetics, 75: 346–353. doi: 10.1111/j.1399-0004.2009.01153.x
- Issue published online: 15 APR 2009
- Article first published online: 17 MAR 2009
- Received 10 September 2008, revised and accepted for publication 1 December 2008
- UROD gene;
- UROD protein
Porphyria cutanea tarda (PCT) arises from decreased hepatic activity of uroporphyrinogen decarboxylase (UROD). Both genetic and environmental factors interplay in the precipitation of clinically overt PCT, but these factors may vary between different geographic areas. Decreased activity of UROD in erythrocytes was used to identify patients with UROD mutations among a group of 130 Spanish PCT patients. Nineteen patients (14.6%) were found to harbor a mutation in the UROD gene. Eight mutations were novel: M1I, 5del10, A22V, D79N, F84I, Q116X, T141I and Y182C. Five others were previously described: F46L, V134Q, R142Q, P150L and E218G. The new missense mutations and P150L were expressed in Escherichia coli. D79N and P150L resulted in proteins that were localized to inclusion bodies. The other mutations produced recombinant proteins that were purified and showed reduced activity (range: 2.3–73.2% of wild type). These single amino acid changes were predicted to produce complex structural alterations and/or reduced stability of the enzyme. Screening of relatives of the probands showed that 37.5% of mutation carriers demonstrated increased urinary porphyrins. This study emphasizes the role of UROD mutations as a strong risk factor for PCT even in areas where environmental factors (hepatitis C virus) have been shown to be highly associated with the disease.