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).

Molecular epidemiology of erythropoietic protoporphyria in the U.K.

“…Our data show that, as in other countries, 6,9,[15][16][17][18][19][20] several different FECH mutations are found in EPP in the U.K. However, allelic heterogeneity is less than for the autosomal dominant acute porphyrias, 21 largely due to the presence of a single large extended family with the mutation c.314 + 2T>G. Similarly high frequencies of a single mutation among apparently unrelated families have been reported for EPP in Northern Ireland, 22 in South Africans of European descent 9 and in Switzerland.…”

Identification of a ferrochelatase mutation in a Chinese family with erythropoietic protoporphyria

“…EPP cases have been reported in Europe [9,10], the United States [11] and Japan [12,13]. The estimated prevalence of symptomatic EPP among Europeans is approximately 1 in 75,000-200,000 individuals, while a much higher prevalence is found in Southeast Asian countries.…”

Case of late‐onset erythropoietic protoporphyria with myelodysplastic syndrome who has homozygous IVS3‐48C polymorphism in the ferrochelatase gene

“…4 Differential diagnoses for EPP include polymorphous light eruption, subacute cutaneous lupus erythematosus, drug-induced phototoxicity, solar urticaria and photoallergy. 3,7,8 The homozygous IVS3-48C polymorphism was found in 19.2% 9 to 22% 10 of the Japanese population. 6 Erythropoietic protoporphyria is generally either an autosomal dominant disorder with incomplete penetrance or an X-linked dominant disorder.…”