title: Erythropoietic protoporphyria: identification of novel mutations in the ferrochelatase gene and comparison of biochemical markers versus molecular analysis as diagnostic strategies.
abstract: BACKGROUND
  Erythropoietic protoporphyria (EPP) results from an inherited deficiency of the last enzyme of the heme biosynthetic pathway, ferrochelatase (FC). EPP is usually inherited in an autosomal dominant fashion, and the mutations in the FC gene on chromosome 18q21.3 detected in EPP patients are heterogeneous.
  
  
  METHODS
  In this study, we screened the FC gene for mutations in 12 patients from 10 unrelated families with EPP and their family members using heteroduplex analysis, automated sequencing, and restriction enzyme digestion.
  
  
  RESULTS
  We detected 8 different mutations in these patients, including 1 missense mutation, 5 frameshift mutations, and 2 splice site mutations, 6 of which are previously undescribed.
  
  
  CONCLUSIONS
  We have established the molecular basis of EPP in 10 unrelated families, thereby providing further evidence for the heterogeneity in this disorder. Importantly, molecular diagnosis allowed revisions in the status of several clinically unaffected silent mutation carriers within the families. We compare the value of genetic research strategies with the combination of biochemical data and clinical phenotype as diagnostic tools to confirm a putative diagnosis in EPP.
authors.affiliation: Department of Dermatology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: J
authors.initials: J
authors.lastname: Frank
authors.forename: J
authors.initials: J
authors.lastname: Nelson
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: W
authors.initials: W
authors.lastname: Ahmad
authors.forename: H
authors.initials: H
authors.lastname: Lam
authors.forename: F K
authors.initials: FK
authors.lastname: Jugert
authors.forename: K
authors.initials: K
authors.lastname: Kalka
authors.forename: M B
authors.initials: MB
authors.lastname: Poh-Fitzpatrick
authors.forename: G
authors.initials: G
authors.lastname: Goerz
authors.forename: H F
authors.initials: HF
authors.lastname: Merk
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D015415:Biomarkers / Q000097:blood; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000032:analysis; D005260:Female; D005294:Ferrochelatase / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D010334:Paternity; D010375:Pedigree; D017121:Porphyria, Hepatoerythropoietic / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D011524:Protoporphyrins / Q000097:blood*
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D011524:Protoporphyrins; D005294:Ferrochelatase