title: 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). EPP is transmitted as an autosomal dominant disorder with an incomplete penetrance. 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.
authors.affiliation: Centre Francais des Porphyries, INSERM U 409, Faculté X. Bichat, Hôpital Louis Mourier, 92701 Colombes Cedex, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gouya
authors.forename: Herve
authors.initials: H
authors.lastname: Puy
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Robreau
authors.forename: Monique
authors.initials: M
authors.lastname: Bourgeois
authors.forename: Jerôme
authors.initials: J
authors.lastname: Lamoril
authors.forename: Vasco
authors.initials: V
authors.lastname: Da Silva
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Deybach
mesh_terms: D001483:Base Sequence; D016373:DNA, Antisense / Q000235:genetics; D005260:Female; D005294:Ferrochelatase / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005602:France / Q000453:epidemiology; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D005799:Genes, Dominant; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D019683:Penetrance; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017092:Porphyria, Erythropoietic / Q000453:epidemiology / Q000235:genetics*; D046351:Protoporphyria, Erythropoietic; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D016373:DNA, Antisense; D022821:RNA Splice Sites; D012333:RNA, Messenger; D005294:Ferrochelatase