Homozygous variegate porphyria: 20 y follow-up and characterization of molecular defect

The long-term follow-up of a homozygous variegate porphyria patient reveale d severe photosensitivity accompanied by mild sensory neuropathy and IgA ne phropathy. A 35T to C transition in exon 2 (I12T) and a 767C to G transvers ion in exon 7 (P256R) of the protoporphyrinogen oxidase gene were identifie d from both alleles of the patient's cDNA and genomic DNA samples. Both pro karyotic and eukaryotic expression studies showed that the first mutation i n the evolutionary conserved region resulted in a decrease in the protoporp hyrinogen oxidase activity in contrast to the polymorphic substitution in e xon 7, which affected the function of the enzyme assayed in Escherichia col i but not COS-1 cells.