Prevalence of deltaF508, G551D, G542X, and R553X mutations among cystic fibrosis patients in the North of Brazil

Abstract

Cystic fibrosis (CF) is the most common genetic disease among Caucasians and is rare among sub-Saharan Africans. The Brazilian population is not ethnically homogeneous but it is the result of threeway ethnic admixture of Europeans, Africans and Amerindians in varying proportions, depending on the region. In the present study, we investigated 33 patients who had been diagnosed and are currently under treatment for CF at the University Hospital João de Barros Barreto, Belém, Pará State. The molecular analysis for G542X, G551D and R553X mutations was performed by PCR followed by RFLP using BstN I, HincII and MboI, respectively, in polyacrylamide gel eletrophoresis and stained with AgNO 3 . The ∆F508 mutation (a deletion of 3 bp) was only analyzed by polyacrylamide gel electrophoresis and stained with AgNO 3 . Each sample was analyzed for regions of interest in the CFTR gene using amplified by PCR and specific primers. The ∆F508 and G551D mutations presented frequencies of 22.7 and 3%, respectively. In 74.3% of the remaining patients, none of the mutations investigated was found. The present study characterized in a sample of patients with an established clinical diagnosis of CF (asthma, repeated bronchopneumonia, disorders of nutritional status, etc.) the most frequent mutation (∆F508) in the North region of Brazil and is also the first report of the G551D mutation. In spite of the wide spectrum of CF mutations and the heterogeneous ethnic origin of the Amazon population, the molecular diagnosis is a helpful additional tool for the diagnosis and treatment of CF patients. Correspondence

CFTR allelic heterogeneity in Brazil: historical and geographical perspectives and implications for screening and counseling for cystic fibrosis in this country

“…In PA, the proportion is reverse of that of RJ: European origin 47%, Amerindians 41% and African origin 12%, 28 suggesting that the lower mutation frequency maybe a result of the mixing of European immigrants with the original populations of the Amazon . 41 The state with the lowest frequency (only 8.68%) is Bahia (BA), the population of which descended mainly from Africans and Portuguese. 42 In this state, only this CF mutation has been studied-its low prevalence may be because of the mixing of African Brazilians with European descendants, mainly Portuguese.…”

Frequency of 8 CFTR gene mutations in cystic fibrosis patients in Minas Gerais, Brazil, diagnosed by neonatal screening

“…According to a recent study, the average estimate of the F508del frequency calculated for five populous Brazilian states is close to 48% (7). Several studies using different molecular biology methods have been published in Brazil showing the mutation profile in some states or regions (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Despite the large variations in ethnic background among different regions, G542X, N1303K and R1162X have been considered to be the most frequent non-F508del mutations in Brazil (6,11,13 …”

Cystic fibrosis and neonatal screening

“…Cabello et al 31 explain the higher frequency of this mutation, 3120+1G A, as the result of the population's ethnic composition in the State of Rio de Janeiro, with a higher proportion of African-descendants. Meanwhile, the G551D mutation, occurring in less than 1% in the State of Rio de Janeiro, was found in 3% of the alleles studied in the State of Pará 26 .…”