Molecular defect in human erythropoietic protoporphyria with fatal liver failure

  title={Molecular defect in human erythropoietic protoporphyria with fatal liver failure},
  author={Yoshitsugu Nakahashi and Hiroaki Miyazaki and Yoichi Kadota and Yuji Naitoh and Kyoichi Inoue and Masayuki Yamamoto and Norio Hayashi and Shigeru Taketani},
  journal={Human Genetics},
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… Expand
Molecular defects in erythropoietic protoporphyria with terminal liver failure
Two new genotypes of EPP are presented, including one with liver failure, a rare and fatal form of E PP, and two new mutations in the ferrochelatase gene are identified in two Swiss patients with erythropoietic protoporphyria. Expand
Human ferrochelatase: a novel mutation in patients with erythropoietic protoporphyria and an isoform caused by alternative splicing
To define the molecular defect in two EPP-affected siblings and their parents in a Swiss family, ferrochelatase cDNA was amplified by the polymerase chain reaction (PCR) and subjected to sequence analysis, revealing autosomal dominant inheritance associated with abnormal protoporphyrin concentration and enzyme activity. Expand
Genetic analysis of the ferrochelatase gene in eight Japanese patients from seven families with erythropoietic protoporphyria
The FECHgene was analyzed in eight Japanese EPP patients from seven non‐consanguineous families and found two distinct genomic DNA abnormalities and intron polymorphism at IVS3‐48, known to be associated with the phenotypic expression of EPP, in these eight patients and 152 healthy Japanese volunteers. Expand
Hypermethylation of the wild-type ferrochelatase allele is closely associated with severe liver complication in a family with erythropoietic protoporphyria.
Results suggest that whereas the combination of a maternal IVS9+1a allele and a paternal IVS3-48c allele results in overt EPP, CpG methylation of the FECH gene promoter increases the severity of E PP, leading to fatal liver failure, as seen in the proband. Expand
Examination of ferrochelatase mutations that cause erythropoietic protoporphyria.
Rec recombinant human ferrochelatase has been engineered to have individual exon deletions corresponding to exons 3 through 11, and one of the human missense mutations, F417S, and a series of amino acid replacements at this site were examined. Expand
Erythropoietic protoporphyria
  • T. Cox
  • Medicine
  • Journal of Inherited Metabolic Disease
  • 2004
The recent development of simple assays for ferrochelatase activity and cloning of the human ferroChelatase gene promises to shed light on the transmission of this disorder and may allow clinical expression of disease to be predicted. Expand
Increased plasma transferrin, altered body iron distribution, and microcytic hypochromic anemia in ferrochelatase-deficient mice.
It is suggested that oral iron therapy is not the therapy of choice for patients with EPP and that the PPIX-liver transferrin pathway plays a role in the orchestration of iron distribution between peripheral iron stores, the spleen, and the bone marrow. Expand
Erythropoietic protoporphyria
  • D. Todd
  • Medicine
  • The British journal of dermatology
  • 1994
Erythropoietic protoporphyria (EPP) is an inherited inborn error of porphyrin metabolism caused by decreased activity of the enzyme ferrochelatase, the terminal enzyme of the haem biosyntheticExpand
Protoporphyria Examination of Ferrochelatase Mutations That Cause Erythropoietic Updated information and services can be found at: (1174 articles) Red Cells • Articles on similar topics can be found in theExpand


The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria.
In Epstein-Barr virus-transformed lymphoblastoid cells from a proband with EPP, enzyme activity, an immunochemically quantifiable protein, and mRNA content of ferrochelatase were about one-half the normal level, suggesting that decreased ferroChelatase mRNA is due to an unstable transcript. Expand
Human erythropoietic protoporphyria: two point mutations in the ferrochelatase gene.
The molecular basis of the ferrochelatase defect responsible for human Erythropoietic Protoporphyria (EPP), a usually autosomal dominant disease, was investigated in a family with an apparently homozygous patient, showing a genetic heterogeneity in EPP. Expand
A molecular defect in human protoporphyria.
Se sequencing of ferrochelatase cDNAs from a patient with protoporphyria revealed a single point mutation resulting in the conversion of a Phe(TTC) to a Ser(TCC) in the carboxy-terminal end of the protein, F417S. Expand
Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease.
A viable autosomal recessive mutation causing jaundice and anemia in mice arose in a mutagenesis experiment using ethylnitrosourea and may represent a model for the human disease, especially in its severe form. Expand
Hereditary hepatic porphyria due to homozygous δ‐aminolevulinic acid dehydratase deficiency: studies in lymphocytes and erythrocytes
Abstract. Activities of δ‐aminolevulinic acid (ALA) dehydratase and porphobilinogen (PBG) deaminase, and haem content were determined in EB‐virus transformed lymphocytes from two patients withExpand
Fatal Liver Failure in Protoporphyria
Liver chemistries deteriorated rapidly when the patient was 63 yr old, with cholestasis precipitated by injury due to excess intake of ethanol, which led to a defect in hepatic protoporphyrin excretion and to further worsening of liver Injury due to porphyrIn deposition. Expand
Molecular cloning and sequence analysis of cDNA encoding human ferrochelatase.
As full-length cDNA for human ferrochelatase is now available, molecular lesions related to erythropoietic protoporphyria can be characterized. Expand
Structure of the human ferrochelatase gene. Exon/intron gene organization and location of the gene to chromosome 18.
Analysis of primer extension showed that the transcription starts at the same position between hepatoma HepG2 and erythroleukemia K562 cell mRNA, thereby suggesting that there can be a single transcript in erythyroid and non-erythroid cells. Expand
Discrimination and quantitative analysis of wild type and point mutant early region 1B genes of adenovirus using oligodeoxyribonucleotide hybridization probes.
Under the stringent wash conditions, the E1B gene of wt Ad2 could be completely discriminated from even a 100-fold molar excess of cyt15 E 1B gene with the 32P-labeled E1 B23 probe. Expand
Ferrochelatase activity in human lymphocytes, as quantified by a new high-performance liquid-chromatographic method.
A new rapid, sensitive high-performance liquid-chromatographic (HPLC) method for determining ferrochelatase (EC 4.1.1) activity in lymphocytes is described and zinc mesoporphyrin formed is extracted with dimethyl sulfoxide-methanol-EDTA for quantification by HPLC. Expand