VARIEGATE PORPHYRIA IN ARGENTINEAN POPULATION. CHARACTERIZARION OF THE MOLECULAR DEFECT

MARIELA FERREIRA GOMES; VICTORIA PARERA; ALCIRA BATLLE ; MARIA VICTORIA ROSSETTI

Congreso; Cape Town Porphyrins and Porphyrias 2005; 2005

Variegate Porhyria (VP) is a low penetrante, autosomal dominant disorder of heme biosynthesis that results from partial deficiency of Protoporphyrinogen oxidase (PPOX). At present 120 diferent 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 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 indentified 8 different mutations in 7 of 12 probands. In order 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 have been reported in American (Chile), German and Dutch families, representing the first demostrable hot spot  mutation in VP. All mutation 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 inicial 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 counsenling for asymptomatic affected individuals.