Digenic Inheritance of Mutations in the Coproporphyrinogen Oxidase and Protoporphyrinogen Oxidase Genes in a Unique Type of Porphyria

Anne Moniek van Tuyll van Serooskerken, Felix W. M. de Rooij, Annie Edixhoven, Reno S. Bladergroen, Jens M. Baron, Sylvia Joussen, Hans F. Merk, Peter M. Steijlen, Pamela Poblete-Gutierrez, Kornelis Te Velde, J. H. Paul Wilson, Rita H. Koole, Michel van Geel, Jorge Frank*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The simultaneous dysfunction of two enzymes within the heme biosynthetic pathway in a single patient is rare. Not more than 15 cases have been reported. A woman with a transient episode of severe photosensitivity showed a biochemical porphyrin profile suggestive of hereditary coproporphyria (HCP), whereas some of her relatives had a profile that was suggestive of variegate porphyria (VP). HCP and VP result from a partial enzymatic deficiency of coproporphyrinogen oxidase (CPOX) and protoporphyrinogen oxidase (PPOX), respectively. DNA analysis in the index patient revealed mutations in both the CPOX and PPOX genes, designated as c.557-15C>G and c. 1289dupT, respectively. The CPOX mutation leads to a cryptic splice site resulting in retention of 14 nucleotides from intron 1 in the mRNA transcript. Both mutations encode null alleles and were associated with nonsense-mediated mRNA decay. Given the digenic inheritance of these null mutations, coupled with the fact that both HCP and VP can manifest with life-threatening acute neurovisceral attacks, the unusual aspect of this case is a relatively mild clinical phenotype restricted to dermal photosensitivity.
Original languageEnglish
Pages (from-to)2249-2254
JournalJournal of Investigative Dermatology
Issue number11
Publication statusPublished - Nov 2011

Cite this