title: Molecular characterization of a ferrochelatase gene defect causing anomalous RNA splicing in erythropoietic protoporphyria.
abstract: Erythropoietic protoporphyria is an inherited disorder caused by deficient activity of the enzyme ferrochelatase. We have examined the ferrochelatase gene in an 11-year-old female with protoporphyria and have found that she is heterozygous for a mutation at a conserved residue in the exon 3 donor splice site consensus sequence (T(+2)-->G). This is inherited from her father, who also has deficient ferrochelatase activity. As a consequence of the mutation, ferrochelatase transcripts are aberrantly spliced and give rise to mRNA molecules in which sequences corresponding to exon 3 are absent. This leads to the expression of a ferrochelatase protein lacking a central region of 40 amino acids.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, U.K.
authors.forename: R P
authors.initials: RP
authors.lastname: Sarkany
authors.forename: D M
authors.initials: DM
authors.lastname: Whitcombe
authors.forename: T M
authors.initials: TM
authors.lastname: Cox
mesh_terms: D001483:Base Sequence; D002648:Child; D018076:DNA, Complementary / Q000032:analysis; D005091:Exons; D005260:Female; D005294:Ferrochelatase / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017121:Porphyria, Hepatoerythropoietic / Q000235:genetics*; D046351:Protoporphyria, Erythropoietic; D012326:RNA Splicing; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; D005294:Ferrochelatase