title: Genetic analysis of the ferrochelatase gene in eight Japanese patients from seven families with erythropoietic protoporphyria.
abstract: 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).
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Kaoshima, Japan. hiroshi.saruwatari@nifty.com
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saruwatari
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ueki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yotsumoto
authors.forename: Tokihiko
authors.initials: T
authors.lastname: Shimada
authors.forename: Seita
authors.initials: S
authors.lastname: Fukumaru
authors.forename: Takuro
authors.initials: T
authors.lastname: Kanekura
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kanzaki
mesh_terms: 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*
chemical_list: D005294:Ferrochelatase