SCREENING FOR FERROCHELATASE MUTATIONS - MOLECULAR HETEROGENEITY OF ERYTHROPOIETIC PROTOPORPHYRIA

The DNA of 21 patients from 19 unrelated families with erythropoietic protoporphyria (EPP) were screened for the 6 ferrochelatase point muta tions so far described. The mutation previously described by us (A >> T transversion at position - 3 of the donor site of intron 10, causing exon 10 skipping) was detected in two additional unrelated EPP patien ts: in these patients, cDNA lacking exon 10 was also detected. The mut ation described by Nakahashi et al. as responsible for exon 2 skipping (C >> T transition at position -23 of the acceptor site of intron 1), although also observed in some normal individuals, was invariably obs erved in all EPP patients tested and may thus play some role in the pa thogenesis of EPP. Thus, it does not appear that this mutation is the primary mechanism underlying exon 2 skipping. None of the other four p reviously described mutations were detected. These data demonstrate th e heterogeneity of the ferrochelatase locus and of the genetic defect in EPP.