Replication Timing Aberration of and / 2 Alleles and Aneuploidy as Markers of Chromosomal Instability and Poor Treatment Response in Ewing Family Tumor Patients.

Replication timing of allelic gene pairs is strictly regulated according to expression, genome stability, and epigenetic changes, and tumorigenesis may be associated with changes in the allelic replication in various tumors. Our aim was to determine whether such alterations had a prognostic value in Ewing's family tumor (EFT) patients. The and / 2β and the centromeric satellite sequence of chromosomes 8 and 12 were used for replication timing assessments.

Identification of single nucleotide variants in SLC26A9 gene in patients with cystic fibrosis (p.Phe508del homozygous) and its association to Orkambi® (Lumacaftor and Ivacaftor) response in vitro.

Background: Since patients with cystic fibrosis with different Cystic Fibrosis Transmembrane Regulator (CFTR) genotypes present a wide response variability for modulator drugs such as Orkambi®, it is important to screen variants in candidate genes with an impact on precision and personalized medicine, such as Solute Carrier Family 26, member 9 (SLC26A9) gene.

Methods: Sanger sequencing for the exons and intron-exon boundary junctions of the SLC26A9 gene was employed in nine individuals with p.Phe508del homozygous genotype for the CFTR gene who were not under CFTR modulators therapy.

Challenges in Diagnosing Primary Ciliary Dyskinesia in a Brazilian Tertiary Hospital.

Primary ciliary dyskinesia (PCD) causes cellular cilia motility alterations, leading to clinical manifestations in the upper and lower respiratory tract and situs abnormalities. The PCD diagnosis was improved after the inclusion of diagnostic tools, such as transmission electron microscopy and genetic screening; however, the PCD screening is a challenge yet. In this context, we aimed to describe the clinical, genetic, and ultra-ciliary characteristics in individuals with clinical suspicion of PCD (cPCD) from a Brazilian Tertiary Hospital.

Single nucleotide variants c.-13G → C (rs17429833) and c.108C → T (rs72466472) in the CLDN1 gene and increased risk for familial colorectal cancer.

Background: The Claudin-1 (CLDN1) protein plays an important role in the function of the tight junction and studies have shown it is aberrantly downregulated in many tumors including colorectal cancer (CRC). The aim of this study was to determine the relationship between four SNVs in the CLDN1 gene [c.-13G → C (rs17429833), c.

A negative screening of rare genetic variants in the ADIPOQ and STATH genes in cystic fibrosis.

Background: The phenotypic variability in cystic fibrosis (CF) is widely recognized and modulated by environmental and genetic factors, including CFTR pathogenic variants and modifier genes genetic variants. In this context, determining the presence of variants in genes involved in immune response may allow a better understanding of CF variability, mainly in lung disease. Thus, ADIPOQ and STATH genes were selected and the analysis of exons and exon/intron junctions was performed for the determination of variations in its sequence, to determine the possible genetic modulation.

Severe pulmonary disease in an adult primary ciliary dyskinesia population in Brazil.

Primary Ciliary Dyskinesia (PCD) is underdiagnosed in Brazil. We enrolled patients from an adult service of Bronchiectasis over a two-year period in a cross-sectional study. The inclusion criteria were laterality disorders (LD), cough with recurrent infections and the exclusion of other causes of bronchiectasis.

Novel, rare and common pathogenic variants in the CFTR gene screened by high-throughput sequencing technology and predicted by in silico tools.

Cystic fibrosis (CF) is caused by ~300 pathogenic CFTR variants. The heterogeneity of which, challenges molecular diagnosis and precision medicine approaches in CF. Our objective was to identify CFTR variants through high-throughput sequencing (HTS) and to predict the pathogenicity of novel variants through in 8 silico tools.

Extent of rescue of F508del-CFTR function by VX-809 and VX-770 in human nasal epithelial cells correlates with SNP rs7512462 in SLC26A9 gene in F508del/F508del Cystic Fibrosis patients.

Background: We analyzed the CFTR response to VX-809/VX-770 drugs in conditionally reprogrammed cells (CRC) of human nasal epithelium (HNE) from F508del/F508del patients based on SNP rs7512462 in the Solute Carrier Family 26, Member 9 (SLC26A9; MIM: 608481) gene.

Methods: The I measurements of primary nasal epithelial cells from F508del/F508del patients (n = 12) for CFTR function were performed in micro Ussing chambers and compared with non-CF controls (n = 2). Data were analyzed according to the rs7512462 genotype which were determined by real-time PCR.

The effect of premature termination codon mutations on CFTR mRNA abundance in human nasal epithelium and intestinal organoids: a basis for read-through therapies in cystic fibrosis.

A major challenge in cystic fibrosis (CF) research is applying mutation-specific therapy to individual patients with diverse and rare CF transmembrane conductance regulator (CFTR) genotypes. Read-through agents are currently the most promising approach for Class I mutations that introduce premature termination codons (PTCs) into CFTR mRNA. However, variations in degradation of PTC containing transcripts by nonsense mediated decay (NMD) might lower read-through efficacy.

Chloride and sodium ion concentrations in saliva and sweat as a method to diagnose cystic fibrosis.

Objective: Cystic fibrosis diagnosis is dependent on the chloride ion concentration in the sweat test (≥60mEq/mL - recognized as the gold standard indicator for cystic fibrosis diagnosis). Moreover, the salivary glands express the CFTR protein in the same manner as sweat glands. Given this context, the objective was to verify the correlation of saliva chloride concentration and sweat chloride concentration, and between saliva sodium concentration and sweat sodium concentration, in patients with cystic fibrosis and healthy control subjects, as a tool for cystic fibrosis diagnosis.

Interaction among variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1, and SLC9A3) and CFTR mutations with clinical markers of cystic fibrosis.

Background: Cystic fibrosis (CF) is due to dysfunction of the CFTR channel and function of this channel is, in turn, affected by modifier genes that can impact the clinical phenotype. In this context, we analyzed the interaction among rs3788766*SLC6A14, rs7512462*SLC26A9, rs17235416*SLC11A1, and rs17563161*SLC9A3 variants, CFTR mutations and 40 CF severity markers by the Multifactor Dimensionality Reduction (MDR) model.

Methods: A total of 164 patients with CF were included in the study.

Association between single nucleotide polymorphisms in TLR4, TLR2, TLR9, VDR, NOS2 and CCL5 genes with acute viral bronchiolitis.

Background: Acute viral bronchiolitis is the leading cause of hospitalization among infants during the first year of life. Most infants hospitalized for bronchiolitis do not present risk factors and are otherwise healthy. Our objective was to determine the genetic features associated with the risk and a severe course of bronchiolitis.

Pancreatic Insufficiency in Cystic Fibrosis: Influence of Inflammatory Response Genes.

Objective: Pancreatic insufficiency (PI) in cystic fibrosis (CF) patients is a crucial clinical marker for severity and disease progression. In our study, 125 modifier genes and their SNPs were associated between CF patients with PI or pancreatic sufficiency.

Methods: We prospectively evaluated 214 CF patients admitted at 1 hospital for a 2-year period.

Cystic fibrosis transmembrane regulator haplotypes in households of patients with cystic fibrosis.

Introduction: Nearly 2000 mutations in the cystic fibrosis transmembrane regulator (CFTR) gene have been reported. The F508del mutation occurs in approximately 50-65% of patients with cystic fibrosis (CF). However, molecular diagnosis is not always possible.

Burkholderia cepacia complex in cystic fibrosis in a Brazilian reference center.

The Burkholderia cepacia complex (BCC) can cause a severe decline in lung function in cystic fibrosis (CF). Our objective was to determine the BCC prevalence and to evaluate its clinical impact on CF. Clinical and laboratory variables were determined for CF patients with BCC (Group-A = 50 patients) and without BCC (Group-B = 134 patients).

Association of clinical severity of cystic fibrosis with variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1 and SLC9A3).

Introduction: Cystic fibrosis (CF) manifests with clinical and histopathological variability depending on environmental and genetic factors. Moreover, the genes encoding ion channels[rs3788766(SLC6A14), rs7512462(SLC26A9), rs17235416(SLC11A1) and rs17563161(SLC9A3)] have been insufficiently studied as modifier genes. Then, our objective was associate the variants in the genes of SLC family with 43 CF severity markers.

Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis.

Objective: Interleukin 8 protein promotes inflammatory responses, even in airways. The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators. Thus, this study analyzed the interleukin 8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to inhaled bronchodilators in cystic fibrosis patients.

Personalized or Precision Medicine? The Example of Cystic Fibrosis.

The advent of the knowledge on human genetics, by the identification of disease-associated variants, culminated in the understanding of human variability. With the genetic knowledge, the specificity of the clinical phenotype and the drug response of each individual were understood. Using the cystic fibrosis (CF) as an example, the new terms that emerged such as personalized medicine and precision medicine can be characterized.

Hypertonic Saline as a Useful Tool for Sputum Induction and Pathogen Detection in Cystic Fibrosis.

Purpose: The aim of this study was to compare the qualitative and semi-quantitative detection of pathogens in the airway secretions of patients with cystic fibrosis (CF) and the sputum induction capacity before and after inhalation of 7% hypertonic saline solution (HSS).

Methods: The study enrolled 64 patients with CF. Airway secretions were collected from all enrolled patients with CF before and after inhalation of 7% HSS, and the samples were screened for pathogens.

Can MTHFR C677T and A1298C Polymorphisms Alter the Risk and Severity of Sporadic Breast Cancer in Brazilian Women?

Introduction: Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) modify the risk and severity of sporadic breast cancer (BC). In this context, the MTHFR C677T and A1298C polymorphisms have been associated with risk and severity of sporadic BC.

Patients And Methods: In total, 253 women with BC and 257 controls were enrolled in this study.