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

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

来源：Journal of Investigative Dermatology, 2011, 131(11): 2249-2254.

DOI：10.1038/jid.2011.186

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.

• 出版日期2011-11