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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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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DOI: https://doi.org/10.1038/ng809
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