D'amato M, Bonuglia M, Barile S, Griso D, Macri A, Sorge F, Biolcati G
Porphyrias Center, S. Gallicano Institute, IRCCS, Rome, Italy
Variegate Porphyria (VP) is one of the acute hepatic porphyrias, and is clinically characterised by skin lesions and acute neuropsychia-tric/visceral attacks that occur separately or together. The disorder is caused by a partial deficiency of protoporphyrinogen oxidase (PPOX), the penultimate enzyme in the heme biosynthetic pathway, and a number of mutations have been described for the corresponding gene PPOX. We report a genetic analysis of VP in Italy, and the identification of eight novel and three previously characterised mutations from thirteen affected individuals. Among those newly identified, two mutations were small deletions (c.418_419delAA; c.759delA), leading to the formation of premature stop codons, two were splicing defects (IVS10+2T>G; IVS12+1G>C), two were nonsense (c.384G>A, c.1013C>G) and three missense mutations (c.848T>A, 202>A, 694>C). This is the first molecular genetics VP study on patients of Italian origin. Finding eight identified novel mutations in thirteen patients confirms the genetic heterogeneity observed for this disorder.