Human erythropoietic protoporphyria: two point mutations in the ferrochelatase gene

The molecular basis of the ferrochelatase defect responsible for human Erythropoietic Protoporphyria (EPP), a usually autosomal dominant disease, was investigated in a family with an apparently homozygous patient. Two mutations of the ferrochelatase gene were identified by sequencing the proband's cDNA after in vitro amplification of the mRNA and subcloning of the amplified products. One mutation results from a G to T transition at nucleotide 163 which produces a glycine to cysteine substitution at amino-acid residue 55 (G-55-C). The other one was a G to A change at nucleotide 801, leading to a methionine to isoleucine substitution at amino-acid residue 267 (M-267-I). This EPP patient was then double heterozygous and as expected each of his parents carried one of the mutations. A second similar EPP patient was screened for these mutations with negative results, showing a genetic heterogeneity in EPP.