title: p.F508del in a heterogeneous cystic fibrosis population from Minas Gerais, Brazil.
abstract: Cystic fibrosis (CF) is the most common autosomal recessive disease of the Caucasian population. Among the various CF mutations, p.F508del is the most frequent, accounting for two-thirds of the global CF chromosomes, although showing great variability among populations. We have studied 115 unrelated CF patients from a mixed population of Minas Gerais (Brazil). To evaluate part of the DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, blood DNA was obtained and PCR was performed using two pairs of primers that anneal to exons 10 and 24 of the CFTR gene. The PCR product was then submitted to automatic sequencing using the ABI PRISM 310 Genetic Analyzer. The p.F508del mutation was found in 50 (21.7%) of 230 unrelated CF alleles. Fifteen (13.0%) patients were homozygous for this mutation, while 20 (17.4%) were heterozygous; the remaining 80 (69.6%) patients did not carry the p.F508del mutation. Exon 24 sequence had no change in 75 (65.2%) patients, 21 (18.3%) had the sequence variation 4521G/A, 11 (9.6%) had a not yet described sequence variation 4407T/A and 8 (7.0%) patients had both sequence variations (4521G/A and 4407T/A). The polymorphism 4407T/A results in an amino acid modification from aspartic acid to glutamic acid, which will probably have no function effect in CFTR. This low p.F508del prevalence can be due to the variable ethnic origin of this population from Minas Gerais, which may have a high diversity of CF rare mutations.
authors.affiliation: Departamento de Anatomia Patológica e Medicina Legal, Universidade Federal de Minas Gerais. pvidigal@medicina.ufmg.br
authors.forename: P V T
authors.initials: PV
authors.lastname: Vidigal
authors.forename: F J C
authors.initials: FJ
authors.lastname: Reis
authors.forename: W L M
authors.initials: WL
authors.lastname: Boson
authors.forename: L A
authors.initials: LA
authors.lastname: De Marco
authors.forename: G
authors.initials: G
authors.lastname: Brasileiro-Filho
mesh_terms: D001938:Brazil / Q000208:ethnology; D003550:Cystic Fibrosis / Q000097:blood / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator