IDENTIFICATION AND CHARACTERIZATION OF A DELETION (537DELAT) IN THE PROTOPORPHYRINOGEN OXIDASE GENE IN A SOUTH-AFRICAN VARIEGATE PORPHYRIA FAMILY

Variegate porphyria is an autosomal dominant disorder of haem metaboli sm resulting from a partial decrease in protoporphyrinogen oxidase act ivity. Variegate porphyria is highly prevalent in South Africa, the re sult of a founder effect now confirmed genetically as a single point m utation (R59W) which has been described in nearly all South African va riegate porphyria patients studied. Only two other mutations (H20P, R1 68C) have been reported in South Africa. We utilised simultaneous, sin gle-stranded conformational polymorphism and heteroduplex analysis, an d direct sequencing to identify a further mutation; a 2 bp deletion in exon 6 which results in a premature stop codon 11 codons downstream f rom the mutation and is the first reported deletion in the protoporphy rinogen oxidase gene in a South African family. The familial segregati on of this mutation strongly suggests that it is the disease causing m utation for variegate porphyria in this family. This further evidence for allelic heterogeneity limits the utility of tests for the R59W mut ation in the diagnosis of variegate porphyria in South Africa. Hum Mut at 12:403-407, 1998. (C) 1998 Wiley Liss, Inc.