Incomplete erythropoietic protoporphyria caused by a splice site modulator homozygous IVS3-48C polymorphism in the...

Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria caused by both the partial deficiency of ferrochelatase (FECH) and the existence of cytosine at IVS3-48 in trans to a mutated FECH allele. However, physicians occasionally encounter patients with EPP with a mild phenotype associated with a slight increase in the erythrocyte-free protoporphyrin concentration and no FECH gene mutations. In this study, genetic analyses were performed on three patients with a mild phenotype of EPP, with photosensitivity, slightly increased erythrocyte-free protoporphyrin concentrations and only a few fluorocytes in the peripheral blood. After obtaining the patients' and their parents' informed consent, a direct sequence analysis of the FECH gene and a restriction fragment length polymorphism analysis were performed on samples from the patients. The FECH gene mutation was not detected in the direct sequence analyses in any of the patients. However, all three patients had the homozygous IVS3-48C polymorphism. These findings suggest that homozygous IVS3-48C polymorphism of the FECH gene is associated with a slight elevation of the protoporphyrin level in erythrocytes, resulting in a mild EPP phenotype.