title: Molecular characterization of erythropoietic protoporphyria in South Africa.
abstract: BACKGROUND
  Erythropoietic protoporphyria (EPP) results from a partial deficiency of ferrochelatase (FECH). Clinical expression normally requires coinheritance of a common hypomorphic FECH allele (IVS3-48C) in trans to a deleterious (primary) FECH mutation.
  
  
  OBJECTIVE
  To characterize South African subjects with EPP, by identification and assessment of FECH sequence variations, including the IVS3-48C polymorphism.
  
  
  METHODS
  Polymerase chain reaction amplification, single-strand conformational polymorphism analysis and restriction endonuclease analysis were employed to identify and determine the frequencies of FECH sequence variations, including the IVS3-48C polymorphism, in a study cohort of symptomatic and asymptomatic South African EPP family members, and a matched control cohort.
  
  
  RESULTS
  We identified 29 patients from 18 families. With the exception of one family, who may represent a phenocopy of EPP, the presentation of EPP was typical. All were of European immigrant stock, and we have not identified EPP in other ethnic groups. Ten sequence variations were identified, including four apparent disease-causing mutations, the IVS3-48T/C polymorphism and five further polymorphisms. The molecular basis of EPP was established for 15 of the 17 families. A 5-bp deletion in exon 7 (757_761delAGAAG) was present in 12 of these families and haplotype studies in these families suggested a single mutational event and thus a local founder effect for this deletion. The other mutations were family specific and included two previously described splice-site mutations (IVS3+2T>G and IVS7+1G>A) and a novel 7-bp deletion in exon 4 (356_362delTTCAAGA).
  
  
  CONCLUSIONS
  The IVS3-48C allele appears to modulate the phenotypic expression of EPP in the South African EPP cohort as observed in other populations.
authors.affiliation: Lennox Eales Porphyria Laboratories, Medical Research Council/University of Cape Town Liver Research Centre, Department of Medicine, University of Cape Town Medical School, Observatory 7925, South Africa.
authors.forename: M
authors.initials: M
authors.lastname: Parker
authors.forename: A V
authors.initials: AV
authors.lastname: Corrigall
authors.forename: R J
authors.initials: RJ
authors.lastname: Hift
authors.forename: P N
authors.initials: PN
authors.lastname: Meissner
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005294:Ferrochelatase / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D046351:Protoporphyria, Erythropoietic / Q000235:genetics*; D013019:South Africa
chemical_list: D005294:Ferrochelatase