Background: Survivors of shipwrecks along the Western Australian coast may have introduced a mutation for variegate porphyria into the Aboriginal population prior to first settlement.
Aims: To assess the mutations responsible for variegate porphyria in Western Australian Aboriginal patients, particularly the R59W mutation, which is the most common cause of variegate porphyria in South Africa.
Methods: New cases of porphyria were diagnosed by biochemical separation of porphyrin subtypes. Single-stranded conformation polymorphism analysis and DNA sequencing of the protoporphyrinogen oxidase gene was performed on Aboriginal patients to define possible causative mutation sites.
Results: Of the 296 new cases of porphyria diagnosed in Western Australia from 1978 to 1998, six had biochemically proven variegate porphyria. Three of those cases occurred in Aboriginal patients. Evidence for a possible fourth Aboriginal case of variegate porphyria is described. The R59W founder mutation responsible for over 90% of variegate porphyria in South Africa was excluded. Two new mutations that predicted amino acid substitutions with significant effects on enzyme function were detected in conserved regions of the protoporphyrinogen oxidase gene in one Aboriginal variegate porphyria patient and the possible fourth case.
Conclusion: Results suggest that the mutations causing variegate porphyria in the Western Australian Aboriginal population occur sporadically and were not inherited from shipwrecked sailors.