Molecular defect in human erythropoietic protoporphyria with fatal liver failure.
We investigated the molecular basis of ferrochelatase in a Japanese patient with erythropoietic protoporphyria (EPP), complicated by fatal liver failure, and defined a novel point mutation in the ferrochelatase gene. cDNAs were synthesized using Epstein-Barr-virus-transformed lymphoblastoid cells from the proband. cDNA clones encoding ferrochelatase in the proband were isolated by amplification using the polymerase chain reaction. There were two sizes of ferrochelatase cDNAs; one was normal in size, the other being smaller. Sequence analysis of the abnormally sized cDNA clones revealed that they lacked exon 9 of the ferrochelatase gene. Genomic DNA analysis demonstrated that the proband had the abnormal allele and that it contained a G to A point mutation at the first position of the donor site of intron 9. An identical mutation was detected in the affected family members of the proband by allele-specific oligonucleotide hybridization analysis. EPP is inherited in an autosomal dominant manner in this family.
Nakahashi
Y
Y
Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Miyazaki
H
H
Kadota
Y
Y
Naitoh
Y
Y
Inoue
K
K
Yamamoto
M
M
Hayashi
N
N
Taketani
S
S
D000328:Adult; D001483:Base Sequence; D002461:Cell Line, Transformed; D004252:DNA Mutational Analysis; D005294:Ferrochelatase / Q000235:genetics*; D017353:Gene Deletion; D005799:Genes, Dominant; D006801:Humans; D017114:Liver Failure, Acute / Q000235:genetics*; D008214:Lymphocytes; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017121:Porphyria, Hepatoerythropoietic / Q000201:enzymology / Q000235:genetics*
D015345:Oligonucleotide Probes; D005294:Ferrochelatase