VARIEGATE PORPHYRIA - IDENTIFICATION OF A NONSENSE MUTATION IN THE PROTOPORPHYRINOGEN OXIDASE GENE

The porphyrias are disorders of porphyrin metabolism that result from inherited or acquired aberrations in the control of the heme biosynthe tic pathway. Variegate porphyria is characterized by a partial reducti on in the activity of protoporphyrinogen oxidase. In this study, we id entified the first nonsense mutation in a family with variegate porphy ria. The mutation consisted of a previously unreported G-to-T transver sion in exon 5 of the protoporphyrinogen oxidase gene, resulting in th e substitution of glutamic acid by a nonsense codon, designated E133X. Our investigation establishes that a nonsense mutation in the protopo rphyrinogen oxidase gene is the underlying mutation in this family wit h variegate porphyria.