Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda.

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: J J Brady, H A Jackson, A G Roberts, R R Morgan, S D Whatley, G L Rowlands, C Darby, E Shudell, R Watson, J Paiker, M W Worwood, G H Elder
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 115 Issue 5 Pg. 868-74 (Nov 2000) ISSN: 0022-202X [Print] United States
• PMID: 11069625 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Uroporphyrinogen Decarboxylase

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Family Health
• Female
• Genotype
• Hemochromatosis (genetics)
• Humans
• Male
• Middle Aged
• Mutation
• Pedigree
• Porphyria Cutanea Tarda (genetics)
• Uroporphyrinogen Decarboxylase (genetics)