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Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda.
J Invest Dermatol. 2000 Nov; 115(5):868-74.JI

Abstract

Porphyria cutanea tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. Mutations in the uroporphyrinogen decarboxylase gene are present in the low-penetrant, autosomal dominant familial form but not in the commoner sporadic form of porphyria cutanea tarda. We have investigated the relationship between age of onset of skin lesions and mutations (C282Y, H63D) in the hemochromatosis gene in familial (19 patients) and sporadic porphyria cutanea tarda (65 patients). Familial porphyria cutanea tarda was identified by mutational analysis of the uroporphyrinogen decarboxylase gene. Five previously described and eight novel mutations (A80S, R144P, L216Q, E218K, L282R, G303S, 402-403delGT, IVS2 + 2 delTAA) were identified. Homozygosity for the C282Y hemochromatosis mutation was associated with an earlier onset of skin lesions in both familial and sporadic porphyria cutanea tarda, the effect being more marked in familial porphyria cutanea tarda where anticipation was demonstrated in family studies. Analysis of the frequencies of hemochromatosis genotypes in each type of porphyria cutanea tarda indicated that C282Y homozygosity is an important susceptibility factor in both types but suggested that heterozygosity for this mutation has much less effect on the development of the disease.

Authors+Show Affiliations

Department of Medical Biochemistry, University Hospital of Wales and University of Wales College of Medicine, Heath Park, Cardiff, UK.No 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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11069625

Citation

Brady, J J., et al. "Co-inheritance of Mutations in the Uroporphyrinogen Decarboxylase and Hemochromatosis Genes Accelerates the Onset of Porphyria Cutanea Tarda." The Journal of Investigative Dermatology, vol. 115, no. 5, 2000, pp. 868-74.
Brady JJ, Jackson HA, Roberts AG, et al. Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda. J Invest Dermatol. 2000;115(5):868-74.
Brady, J. J., Jackson, H. A., Roberts, A. G., Morgan, R. R., Whatley, S. D., Rowlands, G. L., Darby, C., Shudell, E., Watson, R., Paiker, J., Worwood, M. W., & Elder, G. H. (2000). Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda. The Journal of Investigative Dermatology, 115(5), 868-74.
Brady JJ, et al. Co-inheritance of Mutations in the Uroporphyrinogen Decarboxylase and Hemochromatosis Genes Accelerates the Onset of Porphyria Cutanea Tarda. J Invest Dermatol. 2000;115(5):868-74. PubMed PMID: 11069625.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda. AU - Brady,J J, AU - Jackson,H A, AU - Roberts,A G, AU - Morgan,R R, AU - Whatley,S D, AU - Rowlands,G L, AU - Darby,C, AU - Shudell,E, AU - Watson,R, AU - Paiker,J, AU - Worwood,M W, AU - Elder,G H, PY - 2000/11/9/pubmed PY - 2001/2/28/medline PY - 2000/11/9/entrez SP - 868 EP - 74 JF - The Journal of investigative dermatology JO - J. Invest. Dermatol. VL - 115 IS - 5 N2 - Porphyria cutanea tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. Mutations in the uroporphyrinogen decarboxylase gene are present in the low-penetrant, autosomal dominant familial form but not in the commoner sporadic form of porphyria cutanea tarda. We have investigated the relationship between age of onset of skin lesions and mutations (C282Y, H63D) in the hemochromatosis gene in familial (19 patients) and sporadic porphyria cutanea tarda (65 patients). Familial porphyria cutanea tarda was identified by mutational analysis of the uroporphyrinogen decarboxylase gene. Five previously described and eight novel mutations (A80S, R144P, L216Q, E218K, L282R, G303S, 402-403delGT, IVS2 + 2 delTAA) were identified. Homozygosity for the C282Y hemochromatosis mutation was associated with an earlier onset of skin lesions in both familial and sporadic porphyria cutanea tarda, the effect being more marked in familial porphyria cutanea tarda where anticipation was demonstrated in family studies. Analysis of the frequencies of hemochromatosis genotypes in each type of porphyria cutanea tarda indicated that C282Y homozygosity is an important susceptibility factor in both types but suggested that heterozygosity for this mutation has much less effect on the development of the disease. SN - 0022-202X UR - https://www.unboundmedicine.com/medline/citation/11069625/Co_inheritance_of_mutations_in_the_uroporphyrinogen_decarboxylase_and_hemochromatosis_genes_accelerates_the_onset_of_porphyria_cutanea_tarda_ DB - PRIME DP - Unbound Medicine ER -