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The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH

Nature Genetics volume 30, pages 2728 (2002) | Download Citation

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Abstract

Erythropoietic protoporphyria (EPP) is an inherited disorder of heme biosynthesis caused by a partial deficiency of ferrochelatase (FECH, EC 4.99.1.1)1,2. EPP is transmitted as an autosomal dominant disorder3 with an incomplete penetrance1. Using haplotype segregation analysis, we have identified an intronic single nucleotide polymorphism (SNP), IVS3–48T/C, that modulates the use of a constitutive aberrant acceptor splice site. The aberrantly spliced mRNA is degraded by a nonsense-mediated decay mechanism (NMD), producing a decreased steady-state level of mRNA and the additional FECH enzyme deficiency necessary for EPP phenotypic expression.

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Acknowledgements

We thank G. Delrue and J. Grolier (INSERM SCG) for their assistance in preparing the displays.

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Affiliations

  1. Centre Francais des Porphyries, INSERM U 409, Faculté X. Bichat, Hôpital Louis Mourier, 92701 Colombes Cedex, France.

    • Laurent Gouya
    • , Herve Puy
    • , Anne-Marie Robreau
    • , Monique Bourgeois
    • , Jerôme Lamoril
    • , Vasco Da Silva
    • , Bernard Grandchamp
    •  & Jean-Charles Deybach

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jean-Charles Deybach.

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DOI

https://doi.org/10.1038/ng809

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