A novel splicing mutation and haplotype analysis of the FECH gene in a Chinese family with erythropoietic protoporphyria: A novel mutation in EPP

Background Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of haeme biosynthesis resulting from a partial decrease in ferrochelatase (FECH) activity leading to excessive accumulation of protoporphyrin. Clinical manifestation normally requires coinheritance of a common hypomorphic FECH allele and a deleterious FECH mutation. Objective The aim of this study was to characterize the inheritance of a Chinese family with EPP at molecular level, by identification and analysis of FECH sequence variation, including the IVS3-48C polymorphisms. Methods Polymerase chain reaction amplification was employed to identify the FECH sequence variation, including the IVS3-48C polymorphism, in a Chinese EPP family and a matched control cohort. Results A splicing mutation in IVS3 + 1G -> A was identified in the proband as well as his symptomatic sister, cousin, his grandfather and his asymptomatic mother, but was absent in his father and grandmother. All the family members with overt photosensitivity carried the low-expressed allele IVS3-48C, which were absent in the asymptomatic EPP patients of this family. Conclusion We described a novel splicing FECH mutation in a Chinese EPP family and analysed the hypomorphic IVS3-48C allele, which were believed to be responsible for generating the phenotypic symptoms in this family.