title: Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD gene.
abstract: BACKGROUND
  Porphyria cutanea tarda (PCT) results from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. In the majority of patients, the disease is sporadic (S-PCT or type I) and the enzyme deficiency is limited to the liver. Familial PCT (F-PCT or type II) is observed in 20-30% of patients in whom mutations on one allele of the UROD gene reduce UROD activity by approximately 50% in all tissues. Another variant of PCT (type III) is characterized by family history of the disease although it is biochemically indistinguishable from S-PCT.
  
  
  OBJECTIVE
  To investigate the molecular basis of PCT in Spain and to compare enzymatic and molecular analysis for the identification of patients with F-PCT.
  
  
  METHODS
  Erythrocyte UROD activity measurement and mutation analysis of the UROD gene were carried out in a cohort of 61 unrelated Spanish patients with PCT and 50 control individuals. Furthermore, each novel missense mutation identified was characterized by prokaryotic expression studies.
  
  
  RESULTS
  Of these 61 patients, 40 (66%) were classified as having S-PCT, 16 (26%) as having F-PCT and five (8%) as having type III PCT. Discordant results between enzymatic and molecular analysis were observed in two patients with F-PCT. In total, 14 distinct mutations were found, including 10 novel mutations: five missense, one nonsense, three deletions and an insertion. Prokaryotic expression of the novel missense mutations demonstrated that each results in decreased enzyme activity or stability.
  
  
  CONCLUSIONS
  These results confirm the high degree of molecular heterogeneity of F-PCT in Spain and emphasize the usefulness of molecular genetic analysis to distinguish between F-PCT and S-PCT.
authors.affiliation: Research Centre, University Hospital 12 de Octubre, Avda de Córdoba km 5.4, 28041 Madrid, Spain. memendez@h12o.es
authors.forename: M
authors.initials: M
authors.lastname: Méndez
authors.forename: P
authors.initials: P
authors.lastname: Poblete-Gutiérrez
authors.forename: M
authors.initials: M
authors.lastname: García-Bravo
authors.forename: T
authors.initials: T
authors.lastname: Wiederholt
authors.forename: M J
authors.initials: MJ
authors.lastname: Morán-Jiménez
authors.forename: H F
authors.initials: HF
authors.lastname: Merk
authors.forename: M C
authors.initials: MC
authors.lastname: Garrido-Astray
authors.forename: J
authors.initials: J
authors.lastname: Frank
authors.forename: A
authors.initials: A
authors.lastname: Fontanellas
authors.forename: R
authors.initials: R
authors.lastname: Enríquez de Salamanca
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017119:Porphyria Cutanea Tarda / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D012307:Risk Factors; D014575:Uroporphyrinogen Decarboxylase / Q000172:deficiency / Q000235:genetics*
chemical_list: D014575:Uroporphyrinogen Decarboxylase