Academic literature on the topic 'P.Phe508del-CFTR'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'P.Phe508del-CFTR.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "P.Phe508del-CFTR":
1
Dekkers, Johanna F., Ricardo A. Gogorza Gondra, Evelien Kruisselbrink, Annelotte M. Vonk, Hettie M. Janssens, Karin M. de Winter-de Groot, Cornelis K. van der Ent, and Jeffrey M. Beekman. "Optimal correction of distinct CFTR folding mutants in rectal cystic fibrosis organoids." European Respiratory Journal 48, no. 2 (April 21, 2016): 451–58. http://dx.doi.org/10.1183/13993003.01192-2015.
Abstract:
Small-molecule therapies that restore defects in cystic fibrosis transmembrane conductance regulator (CFTR) gating (potentiators) or trafficking (correctors) are being developed for cystic fibrosis (CF) in a mutation-specific fashion. Options for pharmacological correction of CFTR-p.Phe508del (F508del) are being extensively studied but correction of other trafficking mutants that may also benefit from corrector treatment remains largely unknown.We studied correction of the folding mutants CFTR-p.Phe508del, -p.Ala455Glu (A455E) and -p.Asn1303Lys (N1303K) by VX-809 and 18 other correctors (C1–C18) using a functional CFTR assay in human intestinal CF organoids.Function of both CFTR-p.Phe508del and -p.Ala455Glu was enhanced by a variety of correctors but no residual or corrector-induced activity was associated with CFTR-p.Asn1303Lys. Importantly, VX-809-induced correction was most dominant for CFTR-p.Phe508del, while correction of CFTR-p.Ala455Glu was highest by a subgroup of compounds called bithiazoles (C4, C13, C14 and C17) and C5.These data support the development of mutation-specific correctors for optimal treatment of different CFTR trafficking mutants, and identify C5 and bithiazoles as the most promising compounds for correction of CFTR-p.Ala455Glu.
2
Santinelli, Raphaël, Nathalie Benz, Julie Guellec, Fabien Quinquis, Ervin Kocas, Johan Thomas, Tristan Montier, et al. "The Inhibition of the Membrane-Bound Transcription Factor Site-1 Protease (MBTP1) Alleviates the p.Phe508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Defects in Cystic Fibrosis Cells." Cells 13, no. 2 (January 18, 2024): 185. http://dx.doi.org/10.3390/cells13020185.
Abstract:
Cystic Fibrosis (CF) is present due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, the most frequent variant being p.phe508del. The CFTR protein is a chloride (Cl-) channel which is defective and almost absent of cell membranes when the p.Phe508del mutation is present. The p.Phe508del-CFTR protein is retained in the endoplasmic reticulum (ER) and together with inflammation and infection triggers the Unfolded Protein Response (UPR). During the UPR, the Activating Transcription Factor 6 (ATF6) is activated with cleavage and then decreases the expression of p.Phe508del-CFTR. We have previously shown that the inhibition of the activation of ATF6 alleviates the p.Phe508del-CFTR defects in cells overexpressing the mutated protein. In the present paper, our aim was to inhibit the cleavage of ATF6, and thus its activation in a human bronchial cell line with endogenous p.Phe508del-CFTR expression and in bronchial cells from patients, to be more relevant to CF. This was achieved by inhibiting the protease MBTP1 which is responsible for the cleavage of ATF6. We show here that this inhibition leads to increased mRNA and p.Phe508del-CFTR expression and, consequently, to increased Cl-efflux. We also explain the mechanisms linked to these increases with the modulation of genes when MBTP1 is inhibited. Indeed, RT-qPCR assays show that genes such as HSPA1B, CEBPB, VIMP, PFND2, MAPK8, XBP1, INSIG1, and CALR are modulated. In conclusion, we show that the inhibition of MBTP1 has a beneficial effect in relevant models to CF and that this is due to the modulation of genes involved in the disease.
3
Trouvé, Pascal, Claude Férec, and Emmanuelle Génin. "The Interplay between the Unfolded Protein Response, Inflammation and Infection in Cystic Fibrosis." Cells 10, no. 11 (November 2, 2021): 2980. http://dx.doi.org/10.3390/cells10112980.
Abstract:
In cystic fibrosis (CF), p.Phe508del is the most frequent mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. The p.Phe508del-CFTR protein is retained in the ER and rapidly degraded. This retention likely triggers an atypical Unfolded Protein Response (UPR) involving ATF6, which reduces the expression of p.Phe508del-CFTR. There are still some debates on the role of the UPR in CF: could it be triggered by the accumulation of misfolded CFTR proteins in the endoplasmic reticulum as was proposed for the most common CFTR mutation p.Phe508del? Or, is it the consequence of inflammation and infection that occur in the disease? In this review, we summarize recent findings on UPR in CF and show how infection, inflammation and UPR act together in CF. We propose to rethink their respective role in CF and to consider them as a whole.
4
de Faria Poloni, Joice, Thaiane Rispoli, Maria Lucia Rossetti, Cristiano Trindade, and José Eduardo Vargas. "Cystic Fibrosis: Systems Biology Analysis from Homozygous p.Phe508del Variant Patients’ Samples Reveals Perturbations in Tissue-Specific Pathways." BioMed Research International 2021 (December 2, 2021): 1–16. http://dx.doi.org/10.1155/2021/5262000.
Abstract:
Cystic fibrosis (CF) is an autosomal recessive disorder, caused by diverse genetic variants for the CF transmembrane conductance regulator (CFTR) protein. Among these, p.Phe508del is the most prevalent variant. The effects of this variant on the physiology of each tissue remains unknown. This study is aimed at predicting cell signaling pathways present in different tissues of fibrocystic patients, homozygous for p.Phe508del. The study involved analysis of two microarray datasets, E-GEOD-15568 and E-MTAB-360 corresponding to the rectal and bronchial epithelium, respectively, obtained from the ArrayExpress repository. Particularly, differentially expressed genes (DEGs) were predicted, protein-protein interaction (PPI) networks were designed, and centrality and functional interaction networks were analyzed. The study reported that p.Phe508del-mutated CFTR-allele in homozygous state influenced the whole gene expression in each tissue differently. Interestingly, gene ontology (GO) term enrichment analysis revealed that only “neutrophil activation” was shared between both tissues; however, nonshared DEGs were grouped into the same GO term. For further verification, functional interaction networks were generated, wherein no shared nodes were reported between these tissues. These results suggested that the p.Phe508del-mutated CFTR-allele in homozygous state promoted tissue-specific pathways in fibrocystic patients. The generated data might further assist in prediction diagnosis to define biomarkers or devising therapeutic strategies.
5
Tabaripour, Reza, Haleh Akhavan Niaki, Mohammad Reza Esmaeeli Douki, Javad Tavakkoly Bazzaz, Bagher Larijani, and Parichehr Yaghmaei. "Poly Thymidine Polymorphism and Cystic Fibrosis in a Non-Caucasian Population." Disease Markers 32, no. 4 (2012): 241–46. http://dx.doi.org/10.1155/2012/910729.
Abstract:
Background:Cystic fibrosis is a monogenic recessive disorder found predominantly in Caucasian population. This disease arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In this study we consider poly T polymorphism c.1210-12T[5], c.1210-12T[7], c.1210-12T[9] (T5, T7, T9) in the intron 8 of CFTR gene in normal individuals and cystic fibrosis patients in the north of Iran.Material and methods:40 CF patients and 40 normal individuals were screened for poly T polymorphism in intron 8 of CFTR gene using Reverse Dot Blot method which was also used to detect p.Phe508del among CF patients.Results:T7allele is the most prevalent in both normal and CF patients. Its abundance is approximately 75%. T9and T5represent approximately 20% and 5% of alleles respectively. T7/ T7genotype is the most present in both normal and CF patients with 72.5% and 60% prevalence respectively. p.Phe508del was present in 13 CFTR alleles belonging to 7 patients with either homozygote T9/ T9, T7/ T7or compound heterozygote T7/ T9genotypes.Conclusion:Contrary to the Caucasians, T7allele is more frequent in Northern Iranian CF patients. The presence of p.Phe508del and T7allele in the same framework is reported for the first time in this part of the world. Further investigations of other populations will help to understand whether p.Phe508del arose by selection pressure in this part of the world or was imported from European countries. The abundance of T5, T7, T9alleles indicates that this polymorphism can be used as one of the informative markers for detection of normal and mutant alleles in prenatal diagnosis or carrier assessment in families with previous history of the disease in regions with high degree of CFTR mutation heterogeneity.
6
Viart, Victoria, Anne Bergougnoux, Jennifer Bonini, Jessica Varilh, Raphaël Chiron, Olivier Tabary, Nicolas Molinari, Mireille Claustres, and Magali Taulan-Cadars. "Transcription factors and miRNAs that regulate fetal to adult CFTR expression change are new targets for cystic fibrosis." European Respiratory Journal 45, no. 1 (September 3, 2014): 116–28. http://dx.doi.org/10.1183/09031936.00113214.
Abstract:
The CFTR gene displays a tightly regulated tissue-specific and temporal expression. Mutations in this gene cause cystic fibrosis (CF). In this study we wanted to identify trans-regulatory elements responsible for CFTR differential expression in fetal and adult lung, and to determine the importance of inhibitory motifs in the CFTR-3′UTR with the aim of developing new tools for the correction of disease-causing mutations within CFTR.We show that lung development-specific transcription factors (FOXA, C/EBP) and microRNAs (miR-101, miR-145, miR-384) regulate the switch from strong fetal to very low CFTR expression after birth. By using miRNome profiling and gene reporter assays, we found that miR-101 and miR-145 are specifically upregulated in adult lung and that miR-101 directly acts on its cognate site in the CFTR-3′UTR in combination with an overlapping AU-rich element. We then designed miRNA-binding blocker oligonucleotides (MBBOs) to prevent binding of several miRNAs to the CFTR-3′UTR and tested them in primary human nasal epithelial cells from healthy individuals and CF patients carrying the p.Phe508del CFTR mutation. These MBBOs rescued CFTR channel activity by increasing CFTR mRNA and protein levels.Our data offer new understanding of the control of the CFTR gene regulation and new putative correctors for cystic fibrosis.
7
Gramegna, Andrea, Martina Contarini, Stefano Aliberti, Rosaria Casciaro, Francesco Blasi, and Carlo Castellani. "From Ivacaftor to Triple Combination: A Systematic Review of Efficacy and Safety of CFTR Modulators in People with Cystic Fibrosis." International Journal of Molecular Sciences 21, no. 16 (August 16, 2020): 5882. http://dx.doi.org/10.3390/ijms21165882.
Abstract:
Over the last years CFTR (cystic fibrosis transmembrane conductance regulator) modulators have shown the ability to improve relevant clinical outcomes in patients with cystic fibrosis (CF). This review aims at a systematic research of the current evidence on efficacy and tolerability of CFTR modulators for different genetic subsets of patients with CF. Two investigators independently performed the search on PubMed and included phase 2 and 3 clinical trials published in the study period 1 January 2005–31 January 2020. A final pool of 23 papers was included in the systematic review for a total of 4219 patients. For each paper data of interest were extracted and reported in table. In terms of lung function, patients who had the most beneficial effects from CFTR modulation were those patients with one gating mutation receiving IVA (ivacaftor) and patients with p.Phe508del mutation, both homozygous and heterozygous, receiving ELX/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor) had the most relevant beneficial effects in term of lung function, pulmonary exacerbation decrease, and symptom improvement. CFTR modulators showed an overall favorable safety profile. Next steps should aim to systematize our comprehension of scientific data of efficacy and safety coming from real life observational studies.
8
Chernykh, Vyacheslav, Stanislav Krasovsky, Olga Solovova, Tagui Adyan, Anna Stepanova, Ekaterina Marnat, Maria Shtaut, et al. "Pathogenic Variants and Genotypes of the CFTR Gene in Russian Men with Cystic Fibrosis and CBAVD Syndrome." International Journal of Molecular Sciences 24, no. 22 (November 14, 2023): 16287. http://dx.doi.org/10.3390/ijms242216287.
Abstract:
Pathogenic CFTR variants cause cystic fibrosis (CF), and CF-related disorders (CF-RD), including bilateral aplasia of the vas deferens (CBAVD). The spectrum of clinical manifestations depends on the CFTR genotype. The frequency and spectrum of the CFTR variants vary between populations and clinical groups. CFTR variants and genotypes were analyzed in Russian men with CF (n = 546) and CBAVD syndrome (n = 125). Pathogenic variants were detected in 93.95% and 39.2% of the CF and CBAVD alleles, respectively. The most frequent c.1521_1523del (F508del; p.Phe508del) variant was found in 541 (49.5%) CF alleles. A total of 162 CFTR genotypes were revealed in CF patients, including 152 homozygous and 394 compound-heterozygous. The most common CF-genotype was F508del/F508del (24.9%). Other frequent CF-genotypes were F508del/3849+10kbC>T, F508del/CFTRdele2,3, and F508del/E92K. CF-causing variants and/or 5T allele were found in 88% of CBAVD patients: 5T/CFTRmut (48.0%), CFTRmut/N (17.6%), CFTRmut/CFTRmut (6.4%), 5T/5T (10.4%), 5T/N (5.6%) and N/N (12.0%), with the most common CBAVD-genotype being F508del/5T (29.6%). The allele frequencies of F508del, CFTRdele2,3 394delTT, and 3849+10kbC>T were significantly higher in CF patients. L138ins/L138ins, 2184insA/E92K, and L138ins/N genotypes were found in CBAVD, but not in CF patients. The results indicate certain differences in the frequency of some CFTR variants and genotypes in Russian CF and CBAVD patients.
9
Mekki, Chadia, Abdel Aissat, Véronique Mirlesse, Sophie Mayer Lacrosniere, Elsa Eche, Annick Le Floch, Sandra Whalen, et al. "Prenatal Ultrasound Suspicion of Cystic Fibrosis in a Multiethnic Population: Is Extensive CFTR Genotyping Needed?" Genes 12, no. 5 (April 29, 2021): 670. http://dx.doi.org/10.3390/genes12050670.
Abstract:
In families without a Cystic Fibrosis (CF) history, fetal ultrasound bowel abnormalities can unexpectedly reveal the disease. Isolated or in association, the signs can be fetal bowel hyperechogenicity, intestinal loop dilatation and non-visualization of fetal gallbladder. In these cases, search for CF transmembrane conductance regulator (CFTR) gene mutations is part of the recommended diagnostic practices, with a search for frequent mutations according to ethnicity, and, in case of the triad of signs, with an exhaustive study of the gene. However, the molecular diagnosis remains a challenge in populations without well-known frequent pathogenic variants. We present a multiethnic cohort of 108 pregnancies with fetal bowel abnormalities in which the parents benefited from an exhaustive study of the CFTR gene. We describe the new homozygous p.Cys1410* mutation in a fetus of African origin. We did not observe the most frequent p.Phe508del mutation in our cohort but evidenced variants undetected by our frequent mutations kit. Thanks to the progress of sequencing techniques and despite the difficulties of interpretation occasionally encountered, we discuss the need to carry out a comprehensive CFTR study in all patients in case of fetal bowel abnormalities.
10
Neocleous, Vassos, Panayiotis K. Yiallouros, George A. Tanteles, Constantina Costi, Maria Moutafi, Phivos Ioannou, Philippos C. Patsalis, Carolina Sismani, and Leonidas A. Phylactou. "Apparent Homozygosity of p.Phe508del inCFTRdue to a Large Gene Deletion of Exons 4–11." Case Reports in Genetics 2014 (2014): 1–4. http://dx.doi.org/10.1155/2014/613863.
Abstract:
We report a classic cystic fibrosis (CF) boy with a large deletion of exons 4–11 in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on one allele and p.Phe508del in exon 10 on the second allele. Both parents of Georgian and Ukrainian background had no personal or family history of the disease. The initial molecular diagnostic investigation identified the patient as homozygous for the p.Phe508del and not compatible with his parent’s genetic status. The possibility of nonpaternity or uniparental disomy (UPD7) was investigated and excluded using microsatellite analysis of highly polymorphic markers on chromosome 7. Array-CGH was also performed on the patient and revealed a male profile with a subtle deletion within theCFTRgene on the long arm (q-arm) of chromosome 7 (7q31.2). The deletion was confirmed by MLPA extending from probe L02380 to probe L14978 (28.7 kb) and that was inherited from his father, while p.PheF508del was inherited from his mother. These data highlight the need for additional testing for large deletions in patients with apparent homozygosity for a mutatedCFTRallele that do not match the carrier status of the parents. Not testing can lead to misdiagnosis and misinterpretation of mutation carrier status and the expected penetrance of the disorder.
Dissertations / Theses on the topic "P.Phe508del-CFTR":
1
Santinelli, Raphaël. "Inhibition de la voie ATF6 de la réponse aux protéines mal formées comme nouvelle approche thérapeutique dans le cadre de la mucoviscidose." Electronic Thesis or Diss., Brest, 2024. http://www.theses.fr/2024BRES0009.
Abstract:
La mucoviscidose est la maladie génétique létale à transmission autosomale récessive la plus fréquemment retrouvée dans la population européenne. Elle est due à des mutations altérant le gène CFTR, dont la plus fréquente est la mutation induisant la délétion d’une phénylalanine en position 508 de la séquence polypeptidique de cette protéine (p.Phe508del-CFTR). Ces mutations altèrent la viscosité du mucus présent à la surface apicale des cellules épithéliales des systèmes respiratoire, digestif et génital. Cela entraîne une baisse de la clairance mucociliaire, rendant difficile le renouvellement de ce mucus qui est la première barrière protectrice vis-à-vis du développement de microorganismes potentiellement pathogènes. En conséquence, des réponses inflammatoire et infectieuse se mettent en place. En ajoutant l’accumulation de protéines mal repliées dans la lumière du RE, le mécanisme de défense adaptatif UPR est déclenché. ATF6 fait partie de ses trois voies régulatrices. Il a été montré que ATF6 inhibait l’expression du CFTR. Le but de ce projet de thèse est d’évaluer les effets de l’inhibition de la S1P, une protéine centrale pour l’activation de ATF6, sur le p.Phe508del-CFTR par des moyens pharmacologiques. Les résultats montrent que les efflux d’ions Cl- lié à l’activité du canal p.Phe508del-CFTR était augmenté grâce à une augmentation de l’expression globale, ainsi que du transport de ce canal jusqu’à la membrane plasmique. Nous donnons également quelques pistes pouvant expliquer ces effets bénéfiques, notamment en rapport avec le déclenchement de l’UPS qui est une voie permettant le transport de protéines mutées jusqu’à la membrane plasmiqueCystic fibrosis is the most common lethal autosomal recessive genetic disease in the European population. It is caused by mutations in the CFTR gene, the most common of which is the deletion of a phenylalanine at position 508 of the protein's polypeptide sequence (p.Phe508del- CFTR). These mutations alter the viscosity of the mucus present on the apical surface of epithelial cells in the respiratory, digestive and genital systems. This leads to a reduction in mucociliary clearance, making it difficult to renew the mucus that forms the first protective barrier against the development of potentially pathogenic micro- organisms. As a result, inflammatory and infectious responses are triggered. By adding the accumulation of misfolded proteins in the lumen of the ER, the UPR adaptive defence mechanism is triggered. ATF6 is one of its three regulatory pathways. ATF6 has been shown to inhibit CFTR expression. The aim of this thesis project is to evaluate the effects of inhibiting S1P, a protein central for the activation of ATF6, on p.Phe508del-CFTR by pharmacological means. The results show that Cl- ion efflux linked to the activity of the p.Phe508del-CFTR channel is increased through an increase in the overall expression and transport of this channel to the plasma membrane. We also give some possible explanations for these beneficial effects, in particular in relation to the triggering of the UPS, a pathway that allows mutated proteins to be transported to the plasma membrane