PARTIAL CHARACTERIZATION AND ASSIGNMENT OF THE GENE FOR PROTOPORPHYRINOGEN OXIDASE AND VARIEGATE PORPHYRIA TO HUMAN-CHROMOSOME 1Q23

Protoporphyrinogen oxidase (PPO) catalyses the conversion of protoporp hyrinogen IX to protoporphyrin IX, Variegate porphyria (VP), a low-pen etrant, autosomal dominant disorder characterized clinically by skin l esions and neurovisceral attacks, is caused by partial deficiency of t his enzyme, Linkage between VP and the alpha-1-antitrypsin gene on chr omosome 14 has been reported in VP families from South Africa, where t he condition occurs at high frequency due to a founder effect, We have cloned a 4.5 kb genomic DNA fragment containing the entire coding seq uence for human PPO, This clone has been used to localize the human PP O gene to chromosome 1q23 by fluorescence in situ hybridization analys is. The VP gene was mapped by linkage analysis, using microsatellite m arkers spanning the region 1q21-q25.1, in seven British VP families, M ultipoint analysis between VP, SPTA1, APOA2 and D1S194 gave a maximum LOD score of 6.62 at APOA2, which has been physically mapped to 1q21-q 23, Evidence for significant linkage between VP and markers in the alp ha-1-antitrypsin region of chromosome 14 was not obtained. Our results assign the genes for PPO and VP to the same region of chromosome 1, i ndicate that the PPO and VP loci are likely to be the same, and provid e evidence against locus heterogeneity in VP.