Incidence of cystic fibrosis in five different states of Brazil as determined by screening of p.F508del, mutation at the CFTR gene in newborns and patients.

Cystic Fibrosis (CF) is one of the most common single-gene defects in European descent populations with an incidence of about 1 in every 2500 live births and carrier frequency of approximately 1 in 25. The most common mutation at the CF transmembrane conductance regulator (CFTR) gene is a deletion (p.F508del) of the phenylalanine codon 508; its frequency, however, is not the same throughout the world. The purpose of this paper is to document an application of a two-tier survey design in different states of Brazil, from which regional differences of the incidence of CF and frequency of CF-causing mutation(s) carriers can be for the first time estimated. We present data on genotype distributions in reference to p.F508del mutation in samples of newborns, adult controls and CF patients from five Brazilian states, in which a total of 2683 newborns born to Brazilian white parents and 500 African-Brazilians adult controls were screened, as well as 300 CF patients (262 European descents and 38 African descents) were genotyped. Our results suggest that the CF-incidence in different parts of Brazil may differ by almost 20-fold. For the five different states as a whole, nearly 48% of the CF-alleles carry the p.F508del mutation, which places the estimates of disease incidence and carrier frequencies for the Brazilian European descents as 1 in 7576 live births and 2.3%, respectively. The implications for prevention of CF and other rare Mendelian diseases through such surveys of mutation screening are discussed.

High allelic heterogeneity between Afro-Brazilians and Euro-Brazilians impacts cystic fibrosis genetic testing.

Cystic fibrosis (CF) is an autosomal recessive disease caused by at least 1,000 different mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). To determine the frequency of 70 common worldwide CFTR mutations in 155 Euro-Brazilian CF patients and in 38 Afro-Brazilian CF patients, we used direct PCR amplification of DNA from a total of 386 chromosomes from CF patients born in three different states of Brazil. The results show that screening for seventy mutations accounts for 81% of the CF alleles in Euro-Brazilians, but only 21% in the Afro-Brazilian group. We found 21 different mutations in Euro-Brazilians and only 7 mutations in Afro-Brazilians. The frequency of mutations and the number of different mutations detected in Euro-Brazilians are different from Northern European and North American populations, but similar to Southern European populations; in Afro-Brazilians, the mix of CF-mutations is different from those reported in Afro-American CF patients. We also found significant differences in detection rates between Euro-Brazilian (75%) and Afro-Brazilian CF patients (21%) living in the same state, Minas Gerais. These results, therefore, have implications for the use of DNA-based tests for risk assessment in heterogeneous populations like the Brazilians. Further studies are needed to identify the remaining CF mutations in the different populations and regions of Brazil.