title: Molecular epidemiology of erythropoietic protoporphyria in the U.K.
abstract: BACKGROUND
  Erythropoietic protoporphyria (EPP) is a cutaneous porphyria caused by mutations in the ferrochelatase (FECH) or, less frequently, the delta-aminolaevulinate synthase 2 (ALAS2) gene. Predictive genetic counselling requires accurate molecular diagnosis and knowledge of patterns of inheritance.
  
  
  OBJECTIVE
  To investigate the molecular epidemiology of EPP in the U.K.
  
  
  METHODS
  DNA samples from 191 unrelated patients resident in the U.K. were analysed for mutations in the FECH and ALAS2 genes and for the FECH IVS3-48 dimorphism.
  
  
  RESULTS
  Mutations were identified in 179 (94%) patients. Most (169; 94%) had a FECH mutation on one allele and were classified as having pseudodominant EPP (psdEPP); seven (4%) patients had FECH mutations on both alleles (autosomal recessive EPP) and three (2%) patients had ALAS2 mutations (X-linked dominant protoporphyria). The FECH IVS3-48C allele was strongly associated with psdEPP and with the absence of mutations at the FECH or ALAS2 loci. Fifty-six FECH mutations were identified, 19 being previously unreported. Missense mutations were predominant in autosomal recessive EPP (82%) but not in psdEPP (32%). One mutation (c.314 + 2T>G) was present in 41 (24%) of EPP families, most of whom appeared to be descended from a common ancestor resident in the north of England.
  
  
  CONCLUSIONS
  These data define the prevalence and molecular epidemiology of each type of EPP in the U.K.
authors.affiliation: Department of Medical Biochemistry and Immunology, University Hospital of Wales and School of Medicine, Cardiff University, Cardiff CF14 4XN, U.K.
authors.forename: S D
authors.initials: SD
authors.lastname: Whatley
authors.forename: N G
authors.initials: NG
authors.lastname: Mason
authors.forename: S A
authors.initials: SA
authors.lastname: Holme
authors.forename: A V
authors.initials: AV
authors.lastname: Anstey
authors.forename: G H
authors.initials: GH
authors.lastname: Elder
authors.forename: M N
authors.initials: MN
authors.lastname: Badminton
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000235:genetics* / Q000378:metabolism; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005294:Ferrochelatase / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D015995:Prevalence; D046351:Protoporphyria, Erythropoietic / Q000453:epidemiology / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013223:Statistics as Topic; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000624:5-Aminolevulinate Synthetase; D005294:Ferrochelatase