Four novel mutations in the ferrochelatase gene among erythropoietic protoporphyria patients.

A novel mutation was identified by direct sequencing of genomic polymerase chain reaction products in each of four Finnish erythropoietic protoporphyria families. All four mutations, including two deletions (751delGAGAA and the first de novo mutation, 1122delT) and two point mutations (286C-->T and 343C-->T), resulted in a dramatically decreased steady-state level of the allelic transcript, since none of the mutations could be demonstrated by direct sequencing of the amplified cDNAs synthesized from total RNA extracted from patients' lymphoblast cell lines. Because the assays of the ferrochelatase activity and erythrocyte protoporphyrin identify asymptomatic patients poorly, the DNA-based demonstration of a mutation is the only reliable way to screen individuals for the disease-associated mutation.