Genetic analysis of the ferrochelatase gene in eight Japanese patients from seven families with erythropoietic protoporphyria.
A decrease in the activity of ferrochelatase (FECH; EC 4.99.1.1), the terminal enzyme of the heme biosynthetic pathway, results in erythropoietic protoporphyria (EPP; MIM 177000). We analyzed the FECHgene in eight Japanese EPP patients from seven non-consanguineous families and found two distinct genomic DNA abnormalities. In six patients from five families, there was a G-to-A point-mutation at the first position of the intron 9 donor site; it resulted in aberrant splicing and skipping of exon 9 in FECH mRNA. In one patient, we found an A-to-G point-mutation 4 bases from the 3" terminus of intron 4 that led to the in-frame insertion of 3 bases in mRNA. No allelic anomalies, except for 3 single nucleotide polymorphisms were detected in another patient. We analyzed intron polymorphism at IVS3-48, known to be associated with the phenotypic expression of EPP, in these eight patients and 152 healthy Japanese volunteers. All patients were C/C homozygous for IVS3-48. The allelic frequency of IVS3-48C polymorphism in the healthy Japanese volunteers was 67.8% (103/152).
Saruwatari
Hiroshi
H
Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Kaoshima, Japan. hiroshi.saruwatari@nifty.com
Ueki
Yuri
Y
Yotsumoto
Shinichi
S
Shimada
Tokihiko
T
Fukumaru
Seita
S
Kanekura
Takuro
T
Kanzaki
Tamotsu
T
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005294:Ferrochelatase / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D046351:Protoporphyria, Erythropoietic / Q000201:enzymology* / Q000235:genetics*
D005294:Ferrochelatase