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

Raskin, Salmo; Pereira-Ferrari, Lilian; Reis, F.C.; Abreu, Fernando; Maróstica, Paulo José Cauduro; Rozov, Tatiana; Cardieri, Joselina M.; Ludwig, Norberto; Valentin, Lairton; Rosário-Filho, Nelson Augusto; Neto, Eurico Camargo; Lewis, Eduardo; Giugliani, Roberto; Diniz, Edna Maria Albuquerque; Culpi, L.; Phillip, J; Chakraborty, Ranajit

doi:10.1016/j.jcf.2007.03.006

Cited by 77 publications

(61 citation statements)

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“…The G542X, R1162X, and N1303K mutations ΔF508 CFTR gene mutation was the most common mutation found in our study, which corroborates other reports from the same region of Brazil, (16,(22)(23)(24)(25) as well as international reports. (26,27) Other mutations of the CFTR gene, such as R1162X and N1303K, were less common in our CF patients, (22,24,28) as has been reported for CF patients in other parts of the world. (27) The frequencies of the GSTM1 and GSTT1 null genotypes in the CF patients in our study were similar to those found in healthy individuals, in Brazil (29) and elsewhere.…”

Section: Resultssupporting

confidence: 92%

Mutações do gene cystic fibrosis transmembrane conductance regulator e deleções dos genes glutationa S-transferase em pacientes com fibrose cística no Brasil

et al. 2012

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Objective: To determine the effects that mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and deletion of the glutathione S-transferase (GST) genes mu-1 (GSTM1) and theta-1 (GSTT1) have on the clinical course of cystic fibrosis (CF) The null genotypes GSTM1, GSTT1 and GSTM1/GSTT1 were found in 40.9%, 15.2%, and 3.0% of the patients, respectively. The ΔF508 CFTR mutation was more common in patients diagnosed with CF before 2.5 years of age than in those diagnosed later (75.5% vs. 41.2%; p = 0.008). The frequency of the ΔF508 CFTR mutation, as well as of the GSTM1 and GSTT1 genotypes, was not found to be associated with gender, ethnicity, pulmonary disease status, or pancreatic disease status. Conclusions: When the patients were stratified by clinical and epidemiological features, the frequencies of the GSTM1 and GSTT1 null genotypes were similar, suggesting that the inherited absence of these enzymatic pathways does not alter the course of CF. However, the high frequency of the ΔF508 CFTR mutation found in younger children suggests that it influences the age at diagnosis of CF in this region of Brazil.Keywords: Cystic fibrosis; Cystic fibrosis transmembrane conductance regulator; Glutathione transferase. ResumoObjetivo: Determinar os efeitos que a mutação do gene cystic fibrosis transmembrane conductance regulator (CFTR) e da deleção dos genes glutationa S-transferase (GST) mu-1 (GSTM1) e teta-1 (GSTT1) têm na evolução clínica da fibrose cística (FC) em pacientes da região sudeste do Brasil. Métodos: Entre março de 2002 e março de 2005, incluímos no estudo todos os pacientes consecutivos de FC atendidos no Departamento de Pediatria do Hospital de Clínicas da Faculdade de Ciências Médicas da Universidade Estadual de Campinas. O DNA genômico de 66 pacientes com FC foi analisado por reação em cadeia da polimerase e digestão com endonuclease de restrição para a identificação dos genótipos. Resultados: A mutação ΔF508 do gene CFTR foi identificada em 44 (66.7%) pacientes. As deleções dos genes GSTM1, GSTT1 e da combinação nula GSTM1/GSTT1 foram identificadas em 40,9%, 15,2% e 3,0% dos pacientes, respectivamente. A mutação ΔF508 do gene CFTR foi mais comum em pacientes diagnosticados com FC antes dos 2,5 anos de idade que naqueles diagnosticados mais tarde (75,5% vs. 41,2%; p = 0,008). Foram observadas frequências similares da mutação ΔF508 do gene CFTR e dos genótipos GSTM1 e GSTT1 nos pacientes, independentemente do sexo, etnia ou status da doença pulmonar ou pancreática. Conclusões:Quando os pacientes foram estratificados por aspectos clínicos e epidemiológicos, as frequências dos genótipos GSTM1 e GSTT1 nulos foram semelhantes, sugerindo que a ausência herdada dessas vias enzimáticas não altera o curso da FC. Em contraste, a alta frequência da mutação ΔF508 no gene CFTR encontrada em pacientes mais jovens sugere que essa mutação influencia a idade no momento do diagnóstico de FC nessa região do país.Descritores: Fibrose cística; Regulador de condutância transmembrana em fi...

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Section: Resultssupporting

confidence: 92%

Mutações do gene cystic fibrosis transmembrane conductance regulator e deleções dos genes glutationa S-transferase em pacientes com fibrose cística no Brasil

et al. 2012

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“…In Brazil, in view of the genetic diversity of the population (8,38), CF screening by searching for the F508del mutation would not be cost-effective, while searching for the more frequent mutations F508del, G542X, G551D, R553X, and N1303K would probably result in the detection of only one mutated allele and would not permit a diagnosis. On this basis, screening by genetic analysis would have to be planned to detect a larger number of mutations since, as is the case for regions of Southern Europe, especially Spain and Italy, only the search for at least 20 mutations would permit the detection of approximately 70% of affected individuals (9).…”

Section: Discussionmentioning

confidence: 99%

“…A recent study using a two-tier survey design in five Brazilians States (Minas Gerais, São Paulo, Paraná, Santa Catarina, and Rio Grande do Sul) suggested that nearly 48% of the CF alleles carry the F508del mutation and estimated that the disease incidence for Brazilians of European descent is 1 in 7576 live births. In addition, the investigators suggested that the CF prevalence in different parts of Brazil may differ by almost 20-fold (from 1 in 32,258 live births in São Paulo to 1 in 1587 in Rio Grande do Sul) (8).…”

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confidence: 99%

Neonatal screening for cystic fibrosis in São Paulo State, Brazil: a pilot study

Rodrigues

Magalhães

Fernandes

et al. 2009

Braz J Med Biol Res

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70 ng/mL and a 2nd sample was collected from 418 (80.3%) of these patients. Four affected children were detected at two centers, corresponding to an incidence of 1:8403. The average age at diagnosis was 69 days, and 3 of the children already showed severe symptoms of the disease. The rate of false-positive results was 95.2% and the positive predictive value for the test was 8%. The cost of detecting an affected subject was approximately US$8,000.00 when this cystic fibrosis program was added to an existing neonatal screening program. The present study clearly shows the difficulties involved in cystic fibrosis screening using the IRT/IRT protocol, particularly in a population with no long-term tradition of neonatal screening.]]>

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“…In Brazil, the frequency of this mutation, analyzed in the alleles of affected patients, varies from region to region: 49% in Rio Grande do Sul 21 27 . A recent study 22 analyzed the frequency of this mutation in European descendents in five Brazilian States (Minas Gerais, São Paulo, Paraná, Santa Catarina, and Rio Grande do Sul) and observed that approximately 48% of the alleles in CF patients carried the ΔF508 mutation and estimated the prevalence of the disease at 1:7,576 live births in European-descendant Brazilians. Due to the country's extensive miscegenation, the study also showed a large regional variation, estimating the mutation's prevalence at 1:32,258 in children born in the State of São Paulo and 1:1,587 in Rio Grande do Sul.…”

Section: Incidencementioning

confidence: 99%

Cystic fibrosis and neonatal screening

et al. 2008

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The clinical and diagnostic aspects of cystic fibrosis have been extensively reviewed, with an emphasis on neonatal screening. This systematic literature review involved a search for relevant contributions in the PubMed and SciELO databases. The first references to cystic fibrosis date to the Middle Ages. Cystic fibrosis is the most frequent autosomal recessive hereditary disease among Caucasians (1:2,000 to 3,500). More than 1,000 mutations lead to the disease, the most common being "F508, with 70% prevalence among Canadian, Northern European, and American Caucasians and 23 to 55% prevalence among Brazilians. The basic defect is in chloride ion secretion. Cystic fibrosis screening has long been controversial, and after almost three decades, there are few nationwide programs (most are regional or local). However, the U.S. Centers for Disease Control and Prevention (CDC) has concluded that screening for cystic fibrosis is justified. The lack of a specific screening test and the ethnic heterogeneity of the Brazilian population pose challenges for neonatal screening.

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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

Cited by 77 publications

References 24 publications

Mutações do gene cystic fibrosis transmembrane conductance regulator e deleções dos genes glutationa S-transferase em pacientes com fibrose cística no Brasil

Mutações do gene cystic fibrosis transmembrane conductance regulator e deleções dos genes glutationa S-transferase em pacientes com fibrose cística no Brasil

Neonatal screening for cystic fibrosis in São Paulo State, Brazil: a pilot study

Cystic fibrosis and neonatal screening

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