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

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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Figure 2: Correlation between FECH activity and the IVS3–48T/C genotype.
Figure 1: The IVS3–48T/C transition modulates the splicing efficiency of a constitutive cryptic acceptor splice site.

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References

  1. Anderson, K.E., Sassa, S., Bishop, D.F. & Desnick, R.J. The Metabolic and Molecular Bases of Inherited Disease 8th edn (eds Scriver, C.R. et al.) 2991–3062 (McGraw Hill, New York, 2001).

    Google Scholar 

  2. Todd, D.J. Br. J. Derm. 131, 751–766 (1994).

    Article  CAS  Google Scholar 

  3. Went, L.N. & Klasen, E.C. Ann. Hum. Genet. 48, 105–117 (1984).

    Article  CAS  Google Scholar 

  4. Gouya, L. et al. Am. J. Hum. Genet. 58, 292–299 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Gouya, L. et al. Blood 6, 2105–2110 (1999).

    Google Scholar 

  6. Lamoril, J., Boulechfar, S., de Verneuil, H., Grandchamp, B., Nordmann, Y. & Deybach, J.C. Biochem. Biophys. Res. Commun. 2, 594–599 (1991).

    Article  Google Scholar 

  7. Sarkany, R.P., Alexander, G.J., Cox, T.M. Lancet 8910, 1394–1396 (1994).

    Article  Google Scholar 

  8. Borrego, S. et al. J. Med. Genet. 36, 771–774 (1999).

    Article  CAS  Google Scholar 

  9. Borrego, S. et al. J. Med. Genet. 37, 572–578 (2000).

    Article  CAS  Google Scholar 

  10. Li, F.M., Lim, C.K. & Peters, T.J. Biomed. Chromatogr . 2, 164–168 (1987).

    Article  CAS  Google Scholar 

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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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Correspondence to Jean-Charles Deybach.

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The authors declare no competing financial interests.

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Gouya, L., Puy, H., Robreau, AM. et al. The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. Nat Genet 30, 27–28 (2002). https://doi.org/10.1038/ng809

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