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Variegate porphyria (VP), one of the acute hepatic porphyrias, results from an autosomal dominantly inherited deficiency of protoporphyrinogen oxidase (PPOX), the seventh enzyme in heme biosynthesis. Affected individuals can develop both cutaneous symptoms and potentially life-threatening neurovisceral attacks. Thirty unrelated VP index patients and families are currently known in the Swiss Porphyrin Reference Laboratory in Zürich. In 16 of a total of 24 genetically tested families, we detected a recurrent mutation in the PPOX gene, designated 1082-1083insC, reflecting a prevalence of 67%. Haplotype analysis revealed that 1082-1083insC arose on a common genetic background and, thus, represents a novel founder mutation in the Swiss population. Knowledge on the carrier status within a family does not only allow for adequate genetic counseling but also for prevention of the potentially life-threatening acute porphyric attacks. Hence, future molecular screening in Swiss VP patients might be facilitated by first seeking for mutation 1082-1083insC.

Background: Variegate porphyria (VP), also known as South African porphyria, is a low-penetrance, autosomal dominant disorder as the result of a partial deficiency of protoporphyrinogen oxidase (PPOX). Clinically, VP is characterised by photosensitivity and neurovisceral attacks whereby the two symptoms can appear separately or together in patients. VP is little known in Switzerland. In this study, we report a clinical, biochemical and mutational study of eight Swiss VP patients and their families., Results: Six of the eight index patients presented with only skin symptoms, and one with only neurological symptoms. Another patient had both skin and neurological symptoms. Faecal porphyrin excretion was elevated in all patients thus enabling diagnosis. Four different mutations including three novel mutations (G11D, 1041-1042 ins T and 1262-1263 ins 22bp) were identified in this cohort. Mutation 1082-1083 ins C, which had been reported in the French VP population, was shared by five apparently unrelated patients of this study., Conclusion: The novel PPOX gene mutations are apparently unique to the Swiss population. Both clinical and biochemical presentations varied considerably even among those patients who carried an identical mutation, which does not favour the existence of a genotype-phenotype correlation in VP.