Michelle Parker , Anne V. Corrigall and Peter N. Meissner

Lennox Eales Porphyria Laboratories, MRC/UCT Liver Research Centre, Department of Medicine, University of Cape Town Medical School, Observatory 7925, South Africa

Background: Erythropoietic protoporphyria (EPP) is an inherited disorder that has been described as autosomal dominant with incomplete penetrance (Todd 1994). Patients present in childhood with photosensitivity as a result of a defect in heme biosynthesis causing accumulation of protoporphyrin (DeLeo et al. 1976). Mutations in ferrochelatase (FECH), the terminal enzyme of the pathway, are observed in both affected and asymptomatic individuals. Affected individuals, however, appear to have an enzyme deficiency of >50%, which has recently been attributed to a common polymorphism (IVS3-48T/C) on the “wildtype” allele that leads to reduced expression of the allele (Gouya et al. 1996; Gouya et al. 2002). Aim: To characterise a cohort of 13 affected South African EPP individuals at molecular level and to assess the frequency of the IVS3-48C polymorphism in this cohort and a control population. Methods: PCR amplification and subsequent single-stranded conformational polymorphism (SSCP) analysis of the coding region and surrounding intronic sequences of FECH was carried out. Fragments showing an altered pattern were sequenced to identify the mutation. Various enzymes were employed in restriction enzyme digestion in order to screen for identified changes including the IVS3-48T/C polymorphism. Results: A novel 7bp deletion in exon 4 of FECH has been identified in a single individual and a previously described 5bp deletion in exon 7 has been observed in eight individuals in the cohort. Both cause a frameshift and a premature stop codon within 100 amino acids of the deletion. A novel change, namely IVS10-61G/A, was identified although the functional significance has yet to be determined. The frequency in the population has not been determined but unaffected control individuals have been shown to carry the change suggesting that it is a common polymorphism. The IVS3-48C polymorphism was found to be present in 11 of the 13 affected individuals and 10.78% of the matched control population. Discussion: The prevalence of the deletion identified in exon 7 for the majority of patients strongly suggests a founder effect in the South African EPP population. Family studies will allow us to determine whether this mutation is indeed the result of a single ancestral event. The low expression allele appears to play a role in the manifestation of the disease in our population as proposed for the French population.


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Gouya L, Deybach JC, Lamoril J, Da Silva V, Beaumont C, Grandchamp B, Nordmann Y (1996) Modulation of the phenotype in dominant erythropoietic protoporphyria by a low expression of the normal ferrochelatase allele. Am J Hum Genet 58: 292-9

Gouya L, Puy H, Robreau AM, Bourgeois M, Lamoril J, Da Silva V, Grandchamp B, Deybach JC (2002) The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. Nat Genet 30: 27-8