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Background: The p.Arg337His mutation of the TP53 is the most frequent germline missense variant associated with cancer described so far in this gene. It is mainly found in the South and Southeastern regions of Brazil, where it has been associated with a high incidence of pediatric adrenocortical (ACT) and choroid plexus tumors. The frequency and geographic distribution of this mutation is largely unknown, except for the Parana State, where a mean prevalence of 0.27% was reported. In the present study, we developed a high-throughput method for p.Arg337His genotyping, what allowed us to determine the frequency and geographic distribution of this mutation in a cohort from the most populous state in Brazil., Methods: Consecutive samples from 31,612 newborns from São Paulo State were screened for p.Arg337His. The allelic discrimination was done by real-time polymerase chain reaction (PCR) and the presence of haplotype A3 in carriers was examined by using allele-specific oligonucleotide PCR, followed by nested-PCR to detect the SNP rs9894946., Results: We found 67 (0.21%) samples positive for this mutation. The highest p.Arg337His frequencies were found in the cities close to the boundary between São Paulo and Minas Gerais State. No association could be found between p.Arg337His and gender, ethnicity, premature birth or twinning. Remarkably, a trend was found between the geographic distribution of p.Arg337His carriers and occurrence of ACT., Conclusion: We presented for the first time the p.Arg337His frequency among individuals unselected for any disease from a subset of the São Paulo State, the most populous in Brazil. The allele discrimination assay we presented here has proven to be a reliable and efficient method for high-throughput genotyping. ACT was found to be a good sentinel cancer to suppose p.Arg337His presence in our region., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Cystic fibrosis is one of the most common autosomal recessive hereditary diseases in the Caucasian population, with an incidence of 1:2000 to 1:3500 liveborns. More than 1000 mutations have been described with the most common being F508del. It has a prevalence of 23-55% within the Brazilian population. The lack of population-based studies evaluating the incidence of cystic fibrosis in São Paulo State, Brazil, and an analysis concerning the costs of implantation of a screening program motivated the present study. A total of 60,000 dried blood samples from Guthrie cards obtained from April 2005 to January 2006 for neonatal screening at 4 reference centers in São Paulo State were analyzed. The immunoreactive trypsinogen (IRT)/IRT protocol was used with the cut-off value being 70 ng/mL. A total of 532 children (0.9%) showed IRT >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.

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.

Newborn screening for sickle cell disease commenced in 1992 in Sao Paulo State and by the end of 2000, the programme covered 78 institutions in 36 municipalities with the screening of 281,884 babies. Initially based on liquid cord blood samples, these are being replaced by dried filter paper capillary samples to ease handling and avoid diagnostic confusion from maternal contamination. The prevalence of sickle cell trait (2.0%) and HbC trait (0.6%) increased significantly between 1996 and 2000, apparently because of improved detection rather than the later introduction of institutions serving populations with higher trait frequencies. There were 29 babies with homozygous sickle cell SS disease and 26 with sickle cell-haemoglobin C (SC) disease, the latter significantly exceeding expectation and possibly attributable to a nonrandom selection of partners. Sickle cell-beta thalassaemia syndromes were proportionately more common than in Jamaica, and it is possible that this results from interaction with other Brazilian populations carrying higher beta thalassaemia gene frequencies. The frequency of abnormal haemoglobins in this population is lower than in Jamaica, but clinically significant sickle cell disease occurred once in every 5527 births, comparable with the frequencies of other significant inborn errors of metabolism.