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.
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Authors | Anne 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 |
Journal | The Journal of investigative dermatology
(J Invest Dermatol)
Vol. 131
Issue 11
Pg. 2249-54
(Nov 2011)
ISSN: 1523-1747 [Electronic] United States |
PMID | 21734717
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Coproporphyrinogen Oxidase
- Protoporphyrinogen Oxidase
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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)
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