Mutation Screening of the Entire Coding Region of the Protoporphyrinogen Oxidase Gene Using Denaturing Gradient Gel Electrophoresis and Denaturing Hplc (Technical Briefs‪)‬

Variegate porphyria (VP) is characterized by decreased activity of protoporphyrinogen oxidase (PPOX), the penultimate enzyme in the heme biosynthetic pathway. VP belongs to the group of mixed porphyrias and presents with both cutaneous manifestations and acute neurovisceral attacks. Genetically, VP is associated with mutations in the gene encoding PPOX and is usually inherited as an autosomal dominant trait with low clinical penetrance (1, 2). Although a few founder mutations predominate in certain populations, VP generally is a heteroallelic disease, with a variety of mutations in the PPOX gene being responsible for the decreased activity of PPOX (3, 4). The 5.5-kb PPOX gene is located on chromosome 1g22-23 and contains 1 noncoding and 12 coding exons (5). To date, 80 different mutations and polymorphisms have been identified in the PPOX gene (3-12). Characterization by mutational analysis of suspected cases of VP should be considered an important clinical diagnostic tool because of the similarities in clinical presentation of VP, porphyria cutanea tarda (PCT), and hereditary coproporphyria. Furthermore, the use of DNA diagnostic methods enables detection of latent or asymptomatic mutation carriers at risk of developing VP.