The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH

Nat Genet. 2002 Jan;30(1):27-8. doi: 10.1038/ng809. Epub 2001 Dec 20.


Erythropoietic protoporphyria (EPP) is an inherited disorder of heme biosynthesis caused by a partial deficiency of ferrochelatase (FECH, EC EPP is transmitted as an autosomal dominant disorder with an incomplete penetrance. Using haplotype segregation analysis, we have identified an intronic single nucleotide polymorphism (SNP), IVS3-48T/C, that modulates the use of a constitutive aberrant acceptor splice site. The aberrantly spliced mRNA is degraded by a nonsense-mediated decay mechanism (NMD), producing a decreased steady-state level of mRNA and the additional FECH enzyme deficiency necessary for EPP phenotypic expression.

MeSH terms

  • Base Sequence
  • DNA, Antisense / genetics
  • Female
  • Ferrochelatase / biosynthesis*
  • Ferrochelatase / genetics
  • Ferrochelatase / physiology
  • France / epidemiology
  • Gene Expression Regulation, Enzymologic*
  • Gene Frequency
  • Genes, Dominant*
  • Genotype
  • Haplotypes
  • Humans
  • Introns / genetics
  • Male
  • Molecular Sequence Data
  • Penetrance*
  • Point Mutation*
  • Polymorphism, Genetic
  • Porphyria, Erythropoietic / epidemiology
  • Porphyria, Erythropoietic / genetics*
  • Protoporphyria, Erythropoietic
  • RNA Splice Sites / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • DNA, Antisense
  • RNA Splice Sites
  • RNA, Messenger
  • Ferrochelatase