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The molecular basis of porphyria cutanea tarda in Chile: identification and functional characterization of mutations in the uroporphyrinogen decarboxylase gene.
Exp Dermatol. 2004 Jun; 13(6):372-9.ED

Abstract

The porphyrias are heterogeneous disorders arising from predominantly inherited catalytic deficiencies of specific enzymes in heme biosynthesis. Porphyria cutanea tarda (PCT) results from a decreased activity of uroporphyrinogen decarboxylase, the fifth enzyme in heme biosynthesis. The disorder represents the only porphyria that is not exclusively inherited monogenetically. In PCT, at least two different types can be distinguished: acquired/sporadic (type I) PCT, in which the enzymatic deficiency is limited to the liver and inherited/familial (type II) PCT, which is inherited as an autosomal dominant trait with a decrease of enzymatic activity in all tissues. In an effort to characterize the molecular basis of PCT in Chile, we identified eight mutations in 18 previously unclassified PCT families by polymerase chain reaction, heteroduplex analysis, and automated sequencing. To study the role of these mutations in disease causality, in vitro expression of all novel missense mutations was studied. Our results indicate that the frequency of familial PCT in Chile is approximately 50%, thus, to our knowledge, representing the highest incidence of familial PCT reported to date. The data further emphasize the molecular heterogeneity in type II PCT and demonstrate the advantages of molecular genetic techniques as a diagnostic tool and in the detection of clinically asymptomatic mutation carriers.

Authors+Show Affiliations

Department of Dermatology and Allergology, University Clinic of the RWTH Aachen, Aachen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15186324

Citation

Poblete-Gutiérrez, Pamela, et al. "The Molecular Basis of Porphyria Cutanea Tarda in Chile: Identification and Functional Characterization of Mutations in the Uroporphyrinogen Decarboxylase Gene." Experimental Dermatology, vol. 13, no. 6, 2004, pp. 372-9.
Poblete-Gutiérrez P, Mendez M, Wiederholt T, et al. The molecular basis of porphyria cutanea tarda in Chile: identification and functional characterization of mutations in the uroporphyrinogen decarboxylase gene. Exp Dermatol. 2004;13(6):372-9.
Poblete-Gutiérrez, P., Mendez, M., Wiederholt, T., Merk, H. F., Fontanellas, A., Wolff, C., & Frank, J. (2004). The molecular basis of porphyria cutanea tarda in Chile: identification and functional characterization of mutations in the uroporphyrinogen decarboxylase gene. Experimental Dermatology, 13(6), 372-9.
Poblete-Gutiérrez P, et al. The Molecular Basis of Porphyria Cutanea Tarda in Chile: Identification and Functional Characterization of Mutations in the Uroporphyrinogen Decarboxylase Gene. Exp Dermatol. 2004;13(6):372-9. PubMed PMID: 15186324.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The molecular basis of porphyria cutanea tarda in Chile: identification and functional characterization of mutations in the uroporphyrinogen decarboxylase gene. AU - Poblete-Gutiérrez,Pamela, AU - Mendez,Manuel, AU - Wiederholt,Tonio, AU - Merk,Hans F, AU - Fontanellas,Antonio, AU - Wolff,Carlos, AU - Frank,Jorge, PY - 2004/6/10/pubmed PY - 2004/12/23/medline PY - 2004/6/10/entrez SP - 372 EP - 9 JF - Experimental dermatology JO - Exp Dermatol VL - 13 IS - 6 N2 - The porphyrias are heterogeneous disorders arising from predominantly inherited catalytic deficiencies of specific enzymes in heme biosynthesis. Porphyria cutanea tarda (PCT) results from a decreased activity of uroporphyrinogen decarboxylase, the fifth enzyme in heme biosynthesis. The disorder represents the only porphyria that is not exclusively inherited monogenetically. In PCT, at least two different types can be distinguished: acquired/sporadic (type I) PCT, in which the enzymatic deficiency is limited to the liver and inherited/familial (type II) PCT, which is inherited as an autosomal dominant trait with a decrease of enzymatic activity in all tissues. In an effort to characterize the molecular basis of PCT in Chile, we identified eight mutations in 18 previously unclassified PCT families by polymerase chain reaction, heteroduplex analysis, and automated sequencing. To study the role of these mutations in disease causality, in vitro expression of all novel missense mutations was studied. Our results indicate that the frequency of familial PCT in Chile is approximately 50%, thus, to our knowledge, representing the highest incidence of familial PCT reported to date. The data further emphasize the molecular heterogeneity in type II PCT and demonstrate the advantages of molecular genetic techniques as a diagnostic tool and in the detection of clinically asymptomatic mutation carriers. SN - 0906-6705 UR - https://www.unboundmedicine.com/medline/citation/15186324/The_molecular_basis_of_porphyria_cutanea_tarda_in_Chile:_identification_and_functional_characterization_of_mutations_in_the_uroporphyrinogen_decarboxylase_gene_ L2 - https://doi.org/10.1111/j.0906-6705.2004.00163.x DB - PRIME DP - Unbound Medicine ER -