Digenic inheritance of mutations in the coproporphyrinogen oxidase and protoporphyrinogen oxidase genes in a unique type of porphyria - PubMed (original) (raw)

Case Reports

. 2011 Nov;131(11):2249-54.

doi: 10.1038/jid.2011.186. Epub 2011 Jul 7.

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

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Case Reports

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

Anne Moniek van Tuyll van Serooskerken et al. J Invest Dermatol. 2011 Nov.

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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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