title: Heterogeneity of mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria.
abstract: Congenital erythropoietic porphyria (CEP) or Günther's disease is an inborn error of heme biosynthesis transmitted as an autosomal recessive trait and characterized by a profound deficiency of uroporphyrinogen III synthase (UROIIIS) activity. We have previously described two missense mutations in the UROIIIS gene, confirming that the primary defect responsible for CEP is a structural alteration of this gene. We have extended our work to 5 additional unrelated families. Two new point mutations, a deletion and an insertion have been found in the messenger RNA. Our study shows that a molecular heterogeneity of the mutations exists in Günther's disease. One mutation (C73R), however, appears to be more frequent than the others. Finally, the different normal and mutated proteins have been expressed in Escherichia coli to determine the consequence of the mutations on the enzyme activity.
authors.affiliation: laboratoire de Génétique Moléculaire, Faculté de Médecine Xavier Bichat, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Boulechfar
authors.forename: V
authors.initials: V
authors.lastname: Da Silva
authors.forename: J C
authors.initials: JC
authors.lastname: Deybach
authors.forename: Y
authors.initials: Y
authors.lastname: Nordmann
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
authors.forename: H
authors.initials: H
authors.lastname: de Verneuil
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002872:Chromosome Deletion; D004247:DNA / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology; D005822:Genetic Vectors; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D011164:Porphyrias / Q000151:congenital / Q000235:genetics*; D014576:Uroporphyrinogen III Synthetase / Q000235:genetics*
chemical_list: D004247:DNA; D014576:Uroporphyrinogen III Synthetase