Variegate Porphyria in Argentina: clinical and molecular analysis

GRANATA BX; PARERA VE; BATLLE A; ROSSETTI MV

Cardiff

Congreso; International Porphyrins and Porphyrias Meeting; 2011

British Association of Dermatologists

Variegate Porphyria (VP) is caused by mutations in the protoporphyrinogen oxidase (PPOX) gene. This disease is an autosomal dominant disorder with incomplete penetrance, associated to a 50% decrease of the enzyme activity. Clinically it is considered to be a mixed porphyria and patients can present acute and/or cutaneous symptoms. So far, we have diagnosed genetically as VP 97 individuals, corresponding to 32 families. In spite of the molecular heterogeneity that characterizes the porphyrias, mutation c.1043insT, described only in our population, is present in 40% of the VP Argentinean families.    This work?s aims were to determine whether the carriers of the mutation c.1043insT have a characteristic clinical profile and if this high prevalence is due to a founder effect or not.    Regarding the first aim, the symptoms of the c.1043insT patients were compared with symptoms presented by patient with other VP causing mutations. We observed that cutaneous manifestations are the most common in c.1043insT patients (8.3%) and other mutations patients (12.4%), followed by mixed symptoms (6.2% and 9.3%) and acute symptoms (2% and 7.2%). Even though no phenotype-genotype correlation has been established for VP our data shows a greater incidence of cutaneous manifestations in the c.1043insT group. However, we can?t establish a relationship between the highly prevalent mutation and VP symptoms because the proportion of c.1043insT patients and other mutations patients is distributed similarly among the three types of clinical manifestations.    Concerning the hypothesis of the founder effect, we studied 7 single nucleotide polymorphisms (SNPs) in c.1043insT patients, other mutations carriers and controls. SNPs were amplified by PCR and automatically sequenced; the allelic frequencies were obtained by allele count. The results obtained (see table below) showed that in our population the SNPs selected have low variability, therefore no haplotype could be specifically associated to the mutation.    In conclusion, there is no particular symptom directly associated to the c.1043insT mutation as well as there is no haplotype that supports the founder effect hypothesis according to the molecular markers analyzed so far. SNP c.1043insT Other mutations Controls -247 A>C 0.16/0.84 0.55/0.45 0.52/0.48 -246 G>T 1/0 1/0 1/0 -240 G>C 1/0 1/0 1/0 -151 G>T 1/0 0.975/0.025 0.975/0.025 -128 C>G 1/0 0.975/0.025 0.975/0.025 IVS2-47 G>C 0.13/0.87 0.425/0.575 0.425/0.575 IVS5-86 C>T 1/0 0.96/0.04 1/0