Identification of an AluY-mediated deletion of exon 5 in the CPOX gene by MLPA analysis in patients with hereditary coproporphyria

Hereditary coproporphyria (HCP) is an autosomal dominantly inherited hepatic porphyria, caused by a mutation in the coproporphyrinogen oxidase (CPOX) gene. The genetic defect leads to a partial defect of CPOX, the sixth enzyme involved in haem biosynthesis. Affected individuals can develop acute life-threatening attacks of neurovisceral symptoms and/or more rarely cutaneous symptoms such as skin fragility and blistering. The identification of the genetic defect in HCP families is of crucial importance to detect the carrier status which allows counselling to prevent possible triggering factors, e.g. certain drugs, alcohol, or fasting. In a total of nine Swedish HCP families, routine gene sequence analysis had identified a causative mutation in only five. In the present study, using an in-house developed synthetic probe set for multiplex ligation-dependent probe amplification (MLPA) analysis, we detected a deletion of the fifth exon in the CPOX gene in the remaining four families. The deletion is 3381 bp in size and has originated by an Alu-mediated mechanism. This finding emphasizes the usefulness of MLPA analysis as a complement to gene sequencing for comprehensive genetic diagnostics in HCP patients.