Genetic analysis of variegate porphyria (VP) in Italy: identification of six novel mutations in the protoporphyrinogen oxidase (PPOX) gene.
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.
D'Amato
Mauro
M
Istituto San Gallicano, IRCCS, Rome, Italy.
Bonuglia
Margherita
M
Barile
Simona
S
Griso
Daniela
D
Macri
Annelisa
A
Biolcati
Gianfranco
G
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
D005420:Flavoproteins; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493978:PPOX protein, human; D050768:Protoporphyrinogen Oxidase