Exonic deletions as a cause of erythropoietic protoporphyria

Abstract

Erythropoietic protoporphyria (EPP) is an inherited disorder that results from partial deficiency of ferrochelatase (FECH), the terminal enzyme of haem biosynthesis. Current methods that examine the exons and their flanking regions of the FECH gene fail to identify mutations in about one in seven of families with EPP. The presence in some families of intragenic deletions that are not identifiable by current methods for sequencing the FECH gene may partly explain the low sensitivity of mutation detection in EPP. Here we describe the identification by gene dosage analysis of a deletion of exons 3 and 4 in a family with EPP in whom a mutation had not been found by sequencing-based methods.