Geographic heterogeneity of 4 common worldwide cystic fibrosis non-DF508 mutations in Brazil

Cystic fibrosis (CF) is an autosomal recessive disease caused by at least 7 50 different mutations in the cystic fibrosis transmembrane conductance reg ulator (CFTR) gene. The frequency of the most common mutation (DF508) in Br azilian patients of European origin is 47%. To determine the frequency of 4 other common CF mutations (G542X, G551D, R553X, and N1303K) in Brazilian p atients of European origin, we used direct polymerase chain reaction (PCR) amplification of DNA obtained from dried blood spots on Guthrie cards. The DNA came from 247 non-DF508 chromosomes from 172 Brazilian CF patients asce rtained from 5 different states of Brazil. The results show that the 4 muta tions account for 17% of the non-DF508 alleles and only 9% of the total num ber of Brazilian CF alleles. Overall, the frequency of each mutation is dif ferent from northern European and North American populations but similar to southern European populations, mainly the Italian and Spanish populations, When Brazilian patients of European origin are grouped according to state of birth, the frequencies of the mutations are significantly different betw een southern and southeastern states of Brazil. Therefore there are serious implications for risk assessment of DNA-based tests in heterogeneous popul ations such as Brazilians, Further studies are needed to identify the remai ning 44% of CF mutations for the different populations and regions of Brazi l.