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Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD gene.
Br J Dermatol. 2007 Sep; 157(3):501-7.BJ

Abstract

BACKGROUND

Porphyria cutanea tarda (PCT) results from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. In the majority of patients, the disease is sporadic (S-PCT or type I) and the enzyme deficiency is limited to the liver. Familial PCT (F-PCT or type II) is observed in 20-30% of patients in whom mutations on one allele of the UROD gene reduce UROD activity by approximately 50% in all tissues. Another variant of PCT (type III) is characterized by family history of the disease although it is biochemically indistinguishable from S-PCT.

OBJECTIVES

To investigate the molecular basis of PCT in Spain and to compare enzymatic and molecular analysis for the identification of patients with F-PCT.

METHODS

Erythrocyte UROD activity measurement and mutation analysis of the UROD gene were carried out in a cohort of 61 unrelated Spanish patients with PCT and 50 control individuals. Furthermore, each novel missense mutation identified was characterized by prokaryotic expression studies.

RESULTS

Of these 61 patients, 40 (66%) were classified as having S-PCT, 16 (26%) as having F-PCT and five (8%) as having type III PCT. Discordant results between enzymatic and molecular analysis were observed in two patients with F-PCT. In total, 14 distinct mutations were found, including 10 novel mutations: five missense, one nonsense, three deletions and an insertion. Prokaryotic expression of the novel missense mutations demonstrated that each results in decreased enzyme activity or stability.

CONCLUSIONS

These results confirm the high degree of molecular heterogeneity of F-PCT in Spain and emphasize the usefulness of molecular genetic analysis to distinguish between F-PCT and S-PCT.

Authors+Show Affiliations

Research Centre, University Hospital 12 de Octubre, Avda de Córdoba km 5.4, 28041 Madrid, Spain. memendez@h12o.esNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

17627795

Citation

Méndez, M, et al. "Molecular Heterogeneity of Familial Porphyria Cutanea Tarda in Spain: Characterization of 10 Novel Mutations in the UROD Gene." The British Journal of Dermatology, vol. 157, no. 3, 2007, pp. 501-7.
Méndez M, Poblete-Gutiérrez P, García-Bravo M, et al. Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD gene. Br J Dermatol. 2007;157(3):501-7.
Méndez, M., Poblete-Gutiérrez, P., García-Bravo, M., Wiederholt, T., Morán-Jiménez, M. J., Merk, H. F., Garrido-Astray, M. C., Frank, J., Fontanellas, A., & Enríquez de Salamanca, R. (2007). Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD gene. The British Journal of Dermatology, 157(3), 501-7.
Méndez M, et al. Molecular Heterogeneity of Familial Porphyria Cutanea Tarda in Spain: Characterization of 10 Novel Mutations in the UROD Gene. Br J Dermatol. 2007;157(3):501-7. PubMed PMID: 17627795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD gene. AU - Méndez,M, AU - Poblete-Gutiérrez,P, AU - García-Bravo,M, AU - Wiederholt,T, AU - Morán-Jiménez,M J, AU - Merk,H F, AU - Garrido-Astray,M C, AU - Frank,J, AU - Fontanellas,A, AU - Enríquez de Salamanca,R, Y1 - 2007/07/11/ PY - 2007/7/14/pubmed PY - 2008/2/6/medline PY - 2007/7/14/entrez SP - 501 EP - 7 JF - The British journal of dermatology JO - Br. J. Dermatol. VL - 157 IS - 3 N2 - BACKGROUND: Porphyria cutanea tarda (PCT) results from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. In the majority of patients, the disease is sporadic (S-PCT or type I) and the enzyme deficiency is limited to the liver. Familial PCT (F-PCT or type II) is observed in 20-30% of patients in whom mutations on one allele of the UROD gene reduce UROD activity by approximately 50% in all tissues. Another variant of PCT (type III) is characterized by family history of the disease although it is biochemically indistinguishable from S-PCT. OBJECTIVES: To investigate the molecular basis of PCT in Spain and to compare enzymatic and molecular analysis for the identification of patients with F-PCT. METHODS: Erythrocyte UROD activity measurement and mutation analysis of the UROD gene were carried out in a cohort of 61 unrelated Spanish patients with PCT and 50 control individuals. Furthermore, each novel missense mutation identified was characterized by prokaryotic expression studies. RESULTS: Of these 61 patients, 40 (66%) were classified as having S-PCT, 16 (26%) as having F-PCT and five (8%) as having type III PCT. Discordant results between enzymatic and molecular analysis were observed in two patients with F-PCT. In total, 14 distinct mutations were found, including 10 novel mutations: five missense, one nonsense, three deletions and an insertion. Prokaryotic expression of the novel missense mutations demonstrated that each results in decreased enzyme activity or stability. CONCLUSIONS: These results confirm the high degree of molecular heterogeneity of F-PCT in Spain and emphasize the usefulness of molecular genetic analysis to distinguish between F-PCT and S-PCT. SN - 0007-0963 UR - https://www.unboundmedicine.com/medline/citation/17627795/Molecular_heterogeneity_of_familial_porphyria_cutanea_tarda_in_Spain:_characterization_of_10_novel_mutations_in_the_UROD_gene_ L2 - https://doi.org/10.1111/j.1365-2133.2007.08064.x DB - PRIME DP - Unbound Medicine ER -