TY - JOUR
T1 - 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
AU - Raskin, Salmo
AU - Pereira-Ferrari, Lilian
AU - Caldeira Reis, Francisco
AU - Abreu, Fernando
AU - Marostica, Paulo
AU - Rozov, Tatiana
AU - Cardieri, Joselina
AU - Ludwig, Norberto
AU - Valentin, Lairton
AU - Rosario-Filho, Nelson Augusto
AU - Camargo Neto, Eurico
AU - Lewis, Eduardo
AU - Giugliani, Roberto
AU - Albuquerque Diniz, Edna Maria
AU - Culpi, Lodercio
AU - Phillip, John Atlas
AU - Chakraborty, Ranajit
N1 - Funding Information:
For sample collection and laboratory testing this work was supported by funds from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq (through a grant to Salmo Raskin). The statistical analyses were conducted using funds from the US National Institutes of Health PHS grant GM 41399. We thank the CF patients, their families, and ABRAM (Associação Brasileira de Apoio a Mucoviscidose) for their efforts in encouraging this work, and SBTN (Sociedade Brasileira de Triagem Neonatal) for releasing the preliminary data of the CF newborn mandatory screening programs recently established in Brazil. The experiments performed in this study comply with the current Brazilian laws.
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - Brazil
KW - Cystic fibrosis
KW - Incidence
KW - Screening
KW - Two-tier DNA
KW - p.F508del
UR - http://www.scopus.com/inward/record.url?scp=38049007046&partnerID=8YFLogxK
U2 - 10.1016/j.jcf.2007.03.006
DO - 10.1016/j.jcf.2007.03.006
M3 - Article
C2 - 17544945
AN - SCOPUS:38049007046
VL - 7
SP - 15
EP - 22
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
SN - 1569-1993
IS - 1
ER -