title: 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.
authors: Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Anne Moniek
authors: AM
authors: van Tuyll van Serooskerken
authors: Felix W
authors: FW
authors: de Rooij
authors: Annie
authors: A
authors: Edixhoven
authors: Reno S
authors: RS
authors: Bladergroen
authors: Jens M
authors: JM
authors: Baron
authors: Sylvia
authors: S
authors: Joussen
authors: Hans F
authors: HF
authors: Merk
authors: Peter M
authors: PM
authors: Steijlen
authors: Pamela
authors: P
authors: Poblete-Gutiérrez
authors: Kornelis
authors: K
authors: te Velde
authors: J H Paul
authors: JH
authors: Wilson
authors: Rita H
authors: RH
authors: Koole
authors: Michel
authors: M
authors: van Geel
authors: Jorge
authors: J
authors: Frank
mesh_terms: D046349:Coproporphyria, Hereditary / Q000235:genetics; D003304:Coproporphyrinogen Oxidase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010787:Photosensitivity Disorders / Q000235:genetics; D046350:Porphyria, Variegate / Q000235:genetics; D011164:Porphyrias / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D050768:Protoporphyrinogen Oxidase / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D003304:Coproporphyrinogen Oxidase; D050768:Protoporphyrinogen Oxidase