title: Identification of two new mutations 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. Six missense mutations in the UROIIIS gene, a deletion and an insertion have already been described in CEP. This work brings further evidence for the heterogeneity in the genetic defect found in CEP. Two new mutations are described, a point mutation (V99A) and a frame-shift mutation (633insA) in the same patient who had a mild to moderate form of Günther's disease. The mutation (V99A) had a detectable residual activity when expressed in Escherichia coli while the insertion (633insA), which introduced a premature stop, had no activity. In the patients studied in our laboratory, the mutation C73R, associated with a severe phenotype, remains the most frequently seen.
authors.affiliation: Département de Biochimie médicale et Biologie moléculaire, Université de Bordeaux II, France.
authors.forename: M
authors.initials: M
authors.lastname: Bensidhoum
authors.forename: C
authors.initials: C
authors.lastname: Ged
authors.forename: I
authors.initials: I
authors.lastname: Hombrados
authors.forename: F
authors.initials: F
authors.lastname: Moreau-Gaudry
authors.forename: R S
authors.initials: RS
authors.lastname: Hift
authors.forename: P
authors.initials: P
authors.lastname: Meissner
authors.forename: E D
authors.initials: ED
authors.lastname: Sturrock
authors.forename: H
authors.initials: H
authors.lastname: de Verneuil
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D018388:Codon, Terminator; D018076:DNA, Complementary; D004912:Erythrocytes / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D016368:Frameshift Mutation; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D017092:Porphyria, Erythropoietic / Q000235:genetics*; D011166:Porphyrins / Q000378:metabolism / Q000652:urine; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015183:Restriction Mapping; D014576:Uroporphyrinogen III Synthetase / Q000235:genetics* / Q000378:metabolism
chemical_list: D018388:Codon, Terminator; D018076:DNA, Complementary; D011166:Porphyrins; D011993:Recombinant Fusion Proteins; D014576:Uroporphyrinogen III Synthetase