Resumo

MORALES-MACHIN, Alisandra et al. Frequency Of Δf508 mutation in Venezuelan patients with Cystic Fibrosis. Invest. clín [online]. 2004, vol.45, n.2, pp.121-130. ISSN 0535-5133.

Abstract Cystic Fibrosis (CF) is the most common and severe autosomal recessive disease in Caucasian populations, with an incidence of 1 in 2500 live births. It is characterized by a generalized disturbance in exocrine glands and it is caused by over one thousand mutations at the cystic fibrosis conductance regulator gene (CFTR) mapped at 7q31. ΔF508 is the most frequent mutation worldwide and it consists in a deletion of the codon that encodes fenilalanine at the 508 protein΄s position. The aim of this study was to determine the frequency of the ΔF508 mutation in Venezuelan patients with CF using the Polymerase Chain Reaction (PCR). We studied thirty patients of twenty eight families who were diagnosed with CF based on their clinical features and sweat chloride level > 60 mEq/l in two determinations. Detection of the mutation was performed from the amplification of a 98 pair of bases (pb) CF gene segment which contains the codon that encodes fenilalanine in the 508 position by PCR. This PCR product is absent in those who have the mutation. The ΔF508 allelic frequency was 26.79%, distributed in six homozygous and seven compound heterozygote ΔF508/X. The reminder mutations (no ΔF508) represent 73.21%. The ΔF508 frequency in our sample is less than the reported in European countries. On the other hand, a ΔF508 frequency highly heterogeneous has been observed in Latin-American countries. This variation results from mixed populations with a different genetic background influenced by external migration and CF molecular alterations, which exists in the analyzed populations. In this study, the ΔF508 mutation comes mainly from grandparents (79.41%) who were born in Mediterranean countries and Colombia, while the no ΔF508 mutations come from grandparents who were born in Venezuela (79.27%) and Colombia (17.07%).

Palavras-chave : Cystic fibrosis; F508 mutation; polymerase chain reaction.