title: Clinical, biochemical, and genetic study of 11 patients with erythropoietic protoporphyria including one with homozygous disease.
abstract: OBJECTIVE
  To study the mutations in the ferrochelatase gene (FECH) and the phenotypic expression of erythropoietic protoporphyria (EPP) in a group of Spanish patients.
  
  
  METHODS
  Case series.
  
  
  METHODS
  University-based hospital.
  
  
  METHODS
  Eleven unrelated patients with EPP and 19 asymptomatic relatives from 10 families.
  
  
  METHODS
  Measurement of protoporphyrin concentration in red blood cells and feces by fluorometry and chromatography. Analysis of the mutations of the FECH gene by single-strand conformation analysis. Expression of mutations in Escherichia coli.
  
  
  RESULTS
  FECH gene mutations were found in all 11 patients. Ten were heterozygous and carried the IVS3-48C low-expression allele. Three novel mutations were found: IVS4 + 1delG, 347-351delC, and 130_147dupl 18. One patient did not present the IVS3-48C polymorphism and was found to harbor a novel A185T missense mutation in both alleles. The familial study confirmed a recessive mode of inheritance of the disease. The A185T mutation showed a residual activity 4% of normal when expressed in E coli. This patient presented cutaneous photosensitivity similar to the heterozygous cases, but a higher protoporphyrin accumulation in erythrocytes, microcytic anemia, and early signs of liver engagement. FECH mutations were found in 10 healthy relatives, none of whom carried the low-expression allele. The frequency of the IVS3-48C allele among 180 nonporphyric Spanish individuals was 5.2%.
  
  
  CONCLUSIONS
  These findings confirm, among a group of Spanish patients, that most cases of EPP result from the coinheritance of IVS3-48C and a mutation in the FECH gene, and also document the existence of patients with mutations in homozygosity that may present a more severe form of the disease.
authors: Department of Dermatology, Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.
authors: Carmen
authors: C
authors: Herrero
authors: Jordi
authors: J
authors: To-Figueras
authors: Celia
authors: C
authors: Badenas
authors: Manuel
authors: M
authors: Méndez
authors: Patricia
authors: P
authors: Serrano
authors: Rafael
authors: R
authors: Enríquez-Salamanca
authors: Mario
authors: M
authors: Lecha
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005294:Ferrochelatase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D046351:Protoporphyria, Erythropoietic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism
chemical_list: D011524:Protoporphyrins; D005294:Ferrochelatase