Porfiria variegata en Chile: identificación de mutaciones en el gen protoporfirinógeno oxidasa y su implicancia diagnóstica

variegate porphyria (vp) results from a hereditary deficiency of protoporphyrinogen oxidase (ppox) that is transmitted in an autosomal dominan fashion. the diagnosis is based on the clinical symptoms and is confirmed biochemically. sometimes, however, these diagnostic tools reveal limitations in establishing the definitive diagnosis of the prevailing type of acute porphyria. in these patients, molecular genetic analyses can be useful. we performed molecular genetic studies in 13 chilean families by pcr amplification of the ppox gene, conformation sensitive gel electrophoresis, and automated dna sequencing. in five symptomatic patients from different families, respectively, the biochemical data confirmed the diagnosis of vp. in seven other families, however, the biochemical studies were not conclusive. furthermore, the original biochemical analysis in one clinically severely affected patient from a further family even suggested the diagnosis of erythropoietic protoporphyria (epp). beside the respective index patients, we studied 78 asymptomatic family members and 50 healthy, unrelated individuals for control purposes. in five families, the previous diagnosis of vp could be confirmed genetically. further, half of the asymptomatic relatives revealed a mutation in the ppox gene, consisting of three missense mutations and two deletion mutations. mutation r168h that had been already described previously in german vp families was found in a chilean family of german origin. further, two novel missense mutations, designated l74p and g232s, could be detected. in four chilean families, we found the deletion 1330deict that had also been previously described in three swedish vp families. the second deletion, 1239deltacac, has not been described anywhere else but chile and could be identified in seven families. one patient who was initially diagnosed with epp turned out to be a compound heterozygote for mutations on both alíeles of the ppox gene. in conclusion, our molecular gene