Frequency of the deltaF508 mutation in 108 cystic fibrosis patients in São Paulo: comparison with reported Brazilian data (original) (raw)
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Clinics, 2005
PURPOSE: To analyze the frequency of the delta F508 (∆F508) deletion mutation in 108 unrelated cystic fibrosis patients and compare the results with the previously reported data for Brazilian patients. Cystic fibrosis is the leading cause of genetic disease in Caucasians, and the ∆F508 deletion is the most common mutation associated with the disease. METHOD: The frequency of the ∆F508 mutation was assessed by means of a polymerase chain reaction (PCR) followed by detection in 8% silver-stained polyacrylamide gels. RESULTS: Twenty-three of 108 patients (21.3%) were homozygous for the ∆F508 deletion, 50 were heterozygous (46.3%), and the remaining 35 (32.4%) were non-carriers. In terms of alleles, there were 96 mutated (96/216 or 44.45%) and 120 wild-type ones (120/216 or 55.5%). CONCLUSION: The 44.45% of affected alleles that were found is higher than the 33% first described in 1993, but slightly lower than the 48% recently reported. Moreover, our data corroborated the idea that the frequency of the ∆F508 mutation is lower in Brazil in comparison to that found in studies carried out in Europe and North American (circa 70.0%), probably due to increased racial miscegenation. These findings must be taken into account before any genetic screening of the population is proposed in Brazil.
Prevalence of F508del Mutation and Evaluation of Molecular Screening for Cystic Fibrosis in Brazil
Caucasian origin and it is a consequence of mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). As established by the Brazilian Health Ministry Unified Health System, people who have a positive immunoreactive trypsin (IRT) result test and a positive sweat test are referred for molecular investigation of the F508del mutation in the CFTR gene. Objective: To verify the frequency of the F508del mutation in the state of Santa Catarina, Brazil, and to identify the requirement for a broader molecular screening to confirm or exclude the diagnosis of cystic fibrosis. Methods: Descriptive, retrospective, cross-sectional study of patients followed at the center of excellence for the treatment of the cystic fibrosis in the state of Santa Catarina between 2002 and 2015. Results: Ninety-four patients with mean age of 7.62 ± 4.08 years were studied; 55.32% of whom male and 94.68% Caucasian. Of the 188 alleles analyzed, a frequency of 92 (48.94%) alleles was observed for the F508del mutation and 96 (51.06%) for other mutations. The genotype frequencies found for F508del/F508del, F508del/another mutation, and another mutation/another mutation genotypes were, respectively: 28.72% (27 patients), 40.43% (38 patients), and 30.85% (29 patients). Hardy-Weinberg equilibrium was calculated and yielded a chi-square value = 3.43 (p = 0.06). The study population was in equilibrium. Conclusions: According to the guidelines of the Brazilian neonatal screening program, the molecular diagnosis be only be confirmed with the presence of two disease-causing mutations in the CFTR gene, one in each allele. In our study, we observed that only 28.72% of patients had a confirmed molecular diagnosis, which allows us to infer that the molecular diagnosis strategy for cystic fibrosis must be restructured in Brazil to provide a diagnostic contribution to the sweat test.
Cystic fibrosis mutations R1162X and 2183AA®G in two southern Brasilian states
Genetics and Molecular Biology, 1999
We screened 79 southern Brazilian patients with cystic fibrosis for the rare cystic fibrosis mutations R1162X and 2183AA→G. Forty-nine patients were born in the State of Paraná (PR) and 30 in the State of Santa Catarina (SC). Two 2183AA→G alleles were found among the SC patients and one among the PR patients. Six R1162X alleles were found among the SC patients and one among the PR patients. Fourteen percent of the alleles found among patients of Italian origin were R1162X, and 7% were 2183AA→G mutations. These mutations, together with ∆F508, were also studied in a sample of 270 normal non-related subjects of Italian origin who have been born in PR. In this sample we found two ∆F508 alleles and one 2183AA→G allele. ∆F508, R1162X and 2183AA→G frequencies were not statistically different from those observed in Italy. Our results demonstrate that it is important to include these mutations in southern Brazilian surveys of cystic fibrosis patients, especially when they are of Italian descent.
ΔF508 mutation screening of healthy individuals from two populations in Espírito Santo State, Brazil
Genetics and Molecular Research, 2016
The DF508 mutation is the most common cause of cystic fibrosis and its prevalence varies worldwide. For instance, up to 20-fold variations in its frequency have been recorded across different areas of Brazil. This study aimed to compare the distribution of DF508 among healthy individuals of admixed Portuguese descent from Espírito Santo (ES), a state in Southeastern Brazil, to that in a subpopulation of Pomeranian descent, considered to be an isolated group in which the European gene pool has been preserved, living in Santa Maria do Jetibá (also in ES). We found this mutation to be present at a frequency of 0.81% among the Pomeranian group, and 0% in the general ES population. No genetic differentiation was noted between the two populations
Brazilian Journal of Medical and Biological Research, 1998
Sixty-one cystic fibrosis patients admitted for check-up or antibiotic treatment were enrolled for genetic and clinical evaluation. Genetic analysis was performed on blood samples stored on neonatal screening cards using PCR techniques to determine the presence of ∆F508 mutations. Clinical evaluation included Shwachman and Chrispin-Norman scores, age at onset of symptoms and diagnosis, spirometry, awake and sleep pulse oximetry, hyponychial angle measurement and presence of chronic Pseudomonas aeruginosa colonization. Eighteen patients (29.5%) were homozygous for the ∆F508 mutation, 26 (42.6%) had one ∆F508 mutation and 17 (27.9%) were noncarriers, corresponding to a 50.8% prevalence of the mutation in the whole population. Analysis by the Kruskal-Wallis test for comparison of genetic status with continuous variables or by the chi-square test and logistic regression for dichotomous variables showed no significant differences between any two groups for α = 0.05. We conclude that genetic status in relation to the ∆F508 mutation is not associated with pulmonary status as evaluated by the above variables.
Cystic fibrosis mutations R1162X and 2183AA ® G in two southern Brasilian states
Genetics and Molecular Biology, 1999
We screened 79 southern Brazilian patients with cystic fibrosis for the rare cystic fibrosis mutations R1162X and 2183AA→G. Forty-nine patients were born in the State of Paraná (PR) and 30 in the State of Santa Catarina (SC). Two 2183AA→G alleles were found among the SC patients and one among the PR patients. Six R1162X alleles were found among the SC patients and one among the PR patients. Fourteen percent of the alleles found among patients of Italian origin were R1162X, and 7% were 2183AA→G mutations. These mutations, together with ∆F508, were also studied in a sample of 270 normal non-related subjects of Italian origin who have been born in PR. In this sample we found two ∆F508 alleles and one 2183AA→G allele. ∆F508, R1162X and 2183AA→G frequencies were not statistically different from those observed in Italy. Our results demonstrate that it is important to include these mutations in southern Brazilian surveys of cystic fibrosis patients, especially when they are of Italian descent.
Frequency of delta F508 in a Mexican sample of cystic fibrosis patients
Journal of Medical Genetics, 1993
This paper reports the frequency of the AF508 mutation in a cohort of 50 Mexican patients with cystic fibrosis (CF). The mutation was detected by PCR mediated site directed mutagenesis. AF508 was found in 39% of CF chromosomes, a frequency lower than that reported in Argentina and Spain. The high rate of CF cases who die undiagnosed, the ethnic origin of Mexican populations, and the limited number of cases studied could account for the low frequency of the AF508 mutation found in this preliminary report. (J Med Genet 1993;30:
Journal of Cystic Fibrosis, 2008
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.
Genetica, 2017
Cystic fibrosis (CF) is a common autosomal recessive disorder, being the p.F508del the most frequent mutation. Also, a nearby restriction fragment length polymorphism (RFLP) named XK (KM19 and XV2C) is non-randomly associated with specific CF alleles. Our aim was to analyze the occurrence of the p.F508del mutation and XK haplotypes in Afro-Brazilians CF patients and controls, since these data is available for the other two main ethnic groups found in Brazil (Euro-Brazilians and Brazilian Amerindians), contributing for the whole comprehension of these haplotypes in the Brazilian population. A total of 103 patients and 54 controls were studied. PCR and PCR-RFLP methodologies were used to identify the presence of the p.F508del and the XK haplotype in the subjects. The combined data show that 84.2% of p.F508del mutation is associated with haplotype B and only 15.8% with haplotype A; no other haplotypes were found to be associated with this mutation. Our data suggest that the occurrence ...