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A novel mutation in the ferrochelatase gene associated with erythropoietic protoporphyria
Author(s) -
Imoto S.,
Tanizawa Y.,
Sato Y.,
Kaku K.,
Oka Y.
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1771.x
Subject(s) - erythropoietic protoporphyria , ferrochelatase , mutation , point mutation , mutant , biology , genetics , gene , heme , protoporphyrin , biochemistry , enzyme , porphyrin
Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by mutations of the ferrochelatase gene. We investigated a Japanese patient with a dominant form of erythropoietic protoporphyria for a ferrochelatase mutation. Sequence analysis of the proband's ferrochelatase cDNA revealed a T to C point mutation at nucleotide 557. This mutation resulted in the replacement of Ile by Thr at amino acid position 186, a novel mutation in erythropoietic protoporphyria. An increase in ferrochelatase activity was not observed in the crude extract of E. coli over‐expressing the mutant protein compared with the control, whereas a marked increase in activity was observed in that over‐expressing the wild type. Prediction of the secondary structure of ferrochelatase suggested that the Ile 186 → Thr mutation changed the original β‐sheet structure to an α helix in the region including amino acid residue of mutation. We conclude that, in this patient, the Ile 186 → Thr mutation had abolished enzyme activity, possibly by disrupting the secondary structure, thereby causing erythropoietic protoporphyria.