EVIDENCE FOR INVOLVEMENT OF A 2ND GENETIC-LOCUS ON CHROMOSOME-11Q IN PORPHYRIN METABOLISM

Chester porphyria is a distinct type of acute porphyria, which shows a biochemical overlap with acute intermittent and variegate porphyrias and has a dual enzyme deficiency of porphobilinogen deaminase (PBGD) a nd protoporphyrinogen oxidase. Linkage analysis in an extensive family with Chester porphyria was undertaken using multiple polymorphic mark ers. A maximum two point Lod score of 5.25 at 0.07 recombination (conf idence interval 0.01 to 0.14) was observed with D11S351, which has bee n localised to 11q23.1. Multipoint linkage analysis confirmed the two point results and gave a maximum Lod score of 7.33 at a distance less than 1 cM proximal to D11S351. PBGD also maps to 11q but four recombin ants could be identified from ten informative meioses in this family u sing a PBGD DNA polymorphism. Thus, a separate locus on 11q appears to be the basis of Chester porphyria.