Mariela Ferreira Gomes, Victoria Parera, Alcira Batlle & Maria Victoria Rossetti

Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP) - CONICET and University of Buenos Aires, Argentina

Variegate Porphyria (VP) is a low penetrance, autosomal dominant disorder of heme biosynthesis that results from partial deficiency of Protoporphyrinogen oxidase (PPOX). At present 120 different mutations in PPOX gene causing VP have been described. VP prevalence is much higher in South Africa (1:300) due to a founder effect. In Europe, the higher prevalences are found in Finland (2:100.000) and Sweden (1:100.000).

Up to date, about 60 individuals representing 49 apparently unrelated Argentinean families have been biochemically diagnosed with VP, giving a prevalence of approximately 1:600.000 inhabitants.

Genetic studies have been performed in 15 of these families. Sequencing analysis identified 8 different mutations in 7 of 12 probands. In other 3 families the mutation was not yet found. Three nucleotide substitutions (R168H, L178V and H106P), a small deletion (delG745), a small insertion (insT1320) and 3 splicing defects (G810®A, G749®A, g3912®c) were found. R168H and delG745 mutations have been previously reported. The occurrence of the missense mutation R168H had been reported in American (Chile), German and Dutch families, representing the first demonstrable hot spot mutation in VP. All mutations were each specific for an individual family except the small insertion (insT1320) which was found in 5 unrelated families suggesting that it might represent a common mutation in Argentina. So, the initial screening to elucidate the genetic defect in VP patients from Argentina includes the insertion search. Haplotype analysis should still be performed to elucidate if the high occurrence of this mutation would be due to a founder effect.

Molecular analysis in those available family members revealed 5 adults and 4 children who were silent carriers of VP trait assessing that molecular techniques represent the most accurate approach to identify unaffected carriers and to also provide accurate genetic counseling for asymptomatic affected individuals.