title: Hepatoerythropoietic porphyria due to a novel mutation in the uroporphyrinogen decarboxylase gene.
abstract: BACKGROUND
  Hepatoerythropoietic porphyria (HEP) is a rare form of porphyria that results from a deficiency of uroporphyrinogen decarboxylase (UROD). The disease is caused by homoallelism or heteroallelism for mutations in the UROD gene.
  
  
  OBJECTIVE
  To study a 19-year-old woman from Equatorial Guinea, one of the few cases of HEP of African descent and to characterize a new mutation causing HEP.
  
  
  METHODS
  Excretion of porphyrins and residual UROD activity in erythrocytes were measured and compared with those of other patients with HEP. The UROD gene of the proband was sequenced and a new mutation identified. The recombinant UROD protein was purified and assayed for enzymatic activity. The change of amino acid mapped to the UROD protein and the functional consequences were predicted.
  
  
  RESULTS
  The patient presented a novel homozygous G170D missense mutation. Porphyrin excretion showed an atypical pattern in stool with a high pentaporphyrin III to isocoproporphyrin ratio. Erythrocyte UROD activity was 42% of normal and higher than the activity found in patients with HEP with a G281E mutation. The recombinant UROD protein showed a relative activity of 17% and 60% of wild-type to uroporphyrinogen I and III respectively. Molecular modelling showed that glycine 170 is located on the dimer interface of UROD, in a loop containing residues 167-172 that are critical for optimal enzymatic activity and that the carboxyl side chain from aspartic acid is predicted to cause negative interactions between the protein and the substrate.
  
  
  CONCLUSIONS
  The results emphasize the complex relationship between the genetic defects and the biochemical phenotype in homozygous porphyria.
authors.affiliation: Biochemistry and Molecular Genetics Department, Hospital Clinic, School of Medicine, IDIBAPS, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain. JTO@clinic.ub.es
authors.forename: J
authors.initials: J
authors.lastname: To-Figueras
authors.forename: J D
authors.initials: JD
authors.lastname: Phillips
authors.forename: J M
authors.initials: JM
authors.lastname: Gonzalez-López
authors.forename: C
authors.initials: C
authors.lastname: Badenas
authors.forename: I
authors.initials: I
authors.lastname: Madrigal
authors.forename: E M
authors.initials: EM
authors.lastname: González-Romarís
authors.forename: C
authors.initials: C
authors.lastname: Ramos
authors.forename: J M
authors.initials: JM
authors.lastname: Aguirre
authors.forename: C
authors.initials: C
authors.lastname: Herrero
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D060005:Genotyping Techniques; D006720:Homozygote; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D017121:Porphyria, Hepatoerythropoietic / Q000235:genetics*; D011994:Recombinant Proteins; D014575:Uroporphyrinogen Decarboxylase / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D014575:Uroporphyrinogen Decarboxylase