HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Digenic inheritance of mutations in the coproporphyrinogen oxidase and protoporphyrinogen oxidase genes in a unique type of porphyria.

Abstract
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.
AuthorsAnne Moniek van Tuyll van Serooskerken, Felix W de Rooij, Annie Edixhoven, Reno S Bladergroen, Jens M Baron, Sylvia Joussen, Hans F Merk, Peter M Steijlen, Pamela Poblete-Gutiérrez, Kornelis te Velde, J H Paul Wilson, Rita H Koole, Michel van Geel, Jorge Frank
JournalThe Journal of investigative dermatology (J Invest Dermatol) Vol. 131 Issue 11 Pg. 2249-54 (Nov 2011) ISSN: 1523-1747 [Electronic] United States
PMID21734717 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Coproporphyrinogen Oxidase
  • Protoporphyrinogen Oxidase
Topics
  • Coproporphyria, Hereditary (genetics)
  • Coproporphyrinogen Oxidase (genetics)
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Photosensitivity Disorders (genetics)
  • Porphyria, Variegate (genetics)
  • Porphyrias (classification, diagnosis, genetics)
  • Protoporphyrinogen Oxidase (genetics)
  • Sequence Deletion (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: