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

AMV van Serooskerken, Rooij, A Edixhoven, RS Bladergroen, JM Baron, S Joussen, HF Merk, PM Steijlen, P Poblete-Gutierrez, KT Velde, J.H.P. Wilson, RH Koole, M van Geel, J Frank

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)


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 languageUndefined/Unknown
Pages (from-to)2249-2254
Number of pages6
JournalJournal of Investigative Dermatology
Issue number11
Publication statusPublished - 2011

Cite this