title: Genetic analysis of variegate porphyria (VP) in Italy: identification of six novel mutations in the protoporphyrinogen oxidase (PPOX) gene.
abstract: Variegate Porphyria (VP) is one of the acute hepatic porphyrias, and is clinically characterised by skin lesions and acute neuropsychiatric/visceral attacks that occur separately or together. The disorder is caused by a partial deficiency of protoporphyrinogen oxidase, the penultimate enzyme in the heme biosynthetic pathway, and a number of mutations have been described for the corresponding gene (PPOX). Here we report a genetic analysis of VP in Italy, and the identification of six novel and three previously characterised mutations from nine affected individuals and families. 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), one was a nonsense (c.384G>A=p.W128X) and one a missense mutation (c.848T>A=I283N). This is the first study of the molecular genetics of Variegate Porphyria in patients of Italian origin, and the finding of six novel mutations out of nine identified confirms the genetic heterogeneity observed for this disorder.
authors.affiliation: Istituto San Gallicano, IRCCS, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
authors.forename: Margherita
authors.initials: M
authors.lastname: Bonuglia
authors.forename: Simona
authors.initials: S
authors.lastname: Barile
authors.forename: Daniela
authors.initials: D
authors.lastname: Griso
authors.forename: Annelisa
authors.initials: A
authors.lastname: Macri
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Biolcati
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005420:Flavoproteins; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009154:Mutation / Q000235:genetics*; D009679:Nuclear Family; D010088:Oxidoreductases / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D017094:Porphyrias, Hepatic / Q000201:enzymology* / Q000235:genetics*; D050768:Protoporphyrinogen Oxidase
chemical_list: D005420:Flavoproteins; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493978:PPOX protein, human; D050768:Protoporphyrinogen Oxidase