Extended haplotype studies in South African and Dutch variegate porphyria families carrying the recurrent p.R59W mutation confirm a common ancestry

Summary Background Variegate porphyria (VP) is due to a partial deficiency of protoporphyrinogen oxidase (PPOX), the seventh enzyme in the haem biosynthetic pathway. Clinically, VP is characterized by photosensitivity and acute neurovisceral attacks that can manifest separately or together in affected individuals. The disease is inherited in an autosomal dominant fashion with incomplete penetrance and PPOX gene mutations associated with VP are usually unique to patients and their families. In South Africa, however, VP is highly prevalent as the result of a founder mutation, designated p.R59W. Previous genealogical and haplotype studies showed a link between South African and Dutch carriers of p.R59W and it was suggested that this mutation was introduced to South Africa by Dutch settlers at the end of the 17th century. Objectives To perform extended haplotype analysis in six South African and Dutch VP families with the p.R59W mutation. Methods Haplotyping of 13 microsatellite markers flanking the PPOX gene on chromosome 1q22‐23 and five informative single nucleotide polymorphisms within and around the gene. Results A core haplotype cosegregated in all families studied. Conclusions Our data deliver further confirmation that the South African and Dutch VP families carrying mutation p.R59W shared a common ancestor. See also the Commentary by Badminton