Uroporphyrinogen decarboxylase: A splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda

J. R. Garey, L. M. Harrison, K. F. Franklin, K. M. Metcalf, E. S. Radisky, J. P. Kushner

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Uroporphyrinogen decarboxylase (URO-D) is a cytosolic heme-biosynthetic enzyme that converts uroporphyrinogen to coproporphyrinogen. Defects at the uroporphyrinogen decarboxylase locus cause the human genetic disease familial porphyria cutanea tarda. A splice site mutation has been found in a pedigree with familial porphyria cutanes tarda that causes exon 6 to be deleted from the mRNA. The intron/exon junctions on either side of exon 6 fall between codons, so the resulting protein is shorter than the normal protein, missing only the amino acids coded by exon 6. The shortened protein lacks catalytic activity, is rapidly degraded when exposed to human lymphocyte lysates, and is not detectable by Western blot analysis in lymphocyte lysates derived from affected individuals. The mutation was detected in five of 22 unrelated familial porphyria cutanea tarda pedigrees tested, so it appears to be common. This is the first splice site mutation to be found at the URO-D locus, the first mutation that causes familial porphyria cutanea tarda to be in more than one pedigree.

Original languageEnglish (US)
Pages (from-to)1416-1422
Number of pages7
JournalJournal of Clinical Investigation
Volume86
Issue number5
DOIs
StatePublished - 1990

Keywords

  • exon skipping
  • genetic disease
  • heme biosynthesis
  • point mutation
  • polymerase chain reaction

ASJC Scopus subject areas

  • Medicine(all)

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