4 NOVEL MUTATIONS IN THE FERROCHELATASE GENE AMONG ERYTHROPOIETIC PROTOPORPHYRIA PATIENTS

A novel mutation was identified by direct sequencing of genomic polyme rase chain reaction products in each of four Finnish erythropoietic pr otoporphyria families. All four mutations, including two deletions (75 1delGAGAA and the first de novo mutation, 1122delT) and two point muta tions (286C --> T and 343C --> T), resulted in a dramatically decrease d steady-state level of the allelic transcript, since none of the muta tions could be demonstrated by direct sequencing of the amplified cDNA s synthesized from total RNA extracted from patients' lymphoblast cell lines, Because the assays of the ferrochelatase activity and erythroc yte protoporphyrin identify asymptomatic patients poorly, the DNA-base d demonstration of a mutation is the only reliable way to screen indiv iduals for the disease-associated mutation.