scholarly journals The c.3140-26A>G Variant of the CFTR Gene in Homozygous State Causes Mild Cystic Fibrosis – Overview of Longitudinal Clinical Data of the Patient Managed in our CF Center and Review of the Literature

2020 ◽  
Vol 67 (2) ◽  
pp. 666-673
Author(s):  
Ana Kotnik Pirš ◽  
Uroš Krivec ◽  
Katarina Trebušak Podkrajšek
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Data ◽  
Cftr Gene ◽  
Review Of The Literature ◽  
Homozygous State

scholarly journals CFTR Cooperative Cis-Regulatory Elements in Intestinal Cells

2021 ◽  
Vol 22 (5) ◽  
pp. 2599
Author(s):  
Mégane Collobert ◽  
Ozvan Bocher ◽  
Anaïs Le Nabec ◽  
Emmanuelle Génin ◽  
Claude Férec ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Gene Regulation ◽  
Genetic Diseases ◽  
Regulatory Elements ◽  
Cftr Gene ◽  
Intestinal Cells ◽  
Cooperative Effects ◽  
Cis Acting ◽  
Study Techniques

About 8% of the human genome is covered with candidate cis-regulatory elements (cCREs). Disruptions of CREs, described as “cis-ruptions” have been identified as being involved in various genetic diseases. Thanks to the development of chromatin conformation study techniques, several long-range cystic fibrosis transmembrane conductance regulator (CFTR) regulatory elements were identified, but the regulatory mechanisms of the CFTR gene have yet to be fully elucidated. The aim of this work is to improve our knowledge of the CFTR gene regulation, and to identity factors that could impact the CFTR gene expression, and potentially account for the variability of the clinical presentation of cystic fibrosis as well as CFTR-related disorders. Here, we apply the robust GWAS3D score to determine which of the CFTR introns could be involved in gene regulation. This approach highlights four particular CFTR introns of interest. Using reporter gene constructs in intestinal cells, we show that two new introns display strong cooperative effects in intestinal cells. Chromatin immunoprecipitation analyses further demonstrate fixation of transcription factors network. These results provide new insights into our understanding of the CFTR gene regulation and allow us to suggest a 3D CFTR locus structure in intestinal cells. A better understand of regulation mechanisms of the CFTR gene could elucidate cases of patients where the phenotype is not yet explained by the genotype. This would thus help in better diagnosis and therefore better management. These cis-acting regions may be a therapeutic challenge that could lead to the development of specific molecules capable of modulating gene expression in the future.

scholarly journals A Peptide-Nucleic Acid Targeting miR-335-5p Enhances Expression of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene with the Possible Involvement of the CFTR Scaffolding Protein NHERF1

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 117
Author(s):  
Anna Tamanini ◽  
Enrica Fabbri ◽  
Tiziana Jakova ◽  
Jessica Gasparello ◽  
Alex Manicardi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Nucleic Acid ◽  
Peptide Nucleic Acid ◽  
Stop Codon ◽  
Scaffolding Protein ◽  
Cftr Gene ◽  
Scaffolding Proteins ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane

(1) Background: Up-regulation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) might be of great relevance for the development of therapeutic protocols for cystic fibrosis (CF). MicroRNAs are deeply involved in the regulation of CFTR and scaffolding proteins (such as NHERF1, NHERF2 and Ezrin). (2) Methods: Content of miRNAs and mRNAs was analyzed by RT-qPCR, while the CFTR and NHERF1 production was analyzed by Western blotting. (3) Results: The results here described show that the CFTR scaffolding protein NHERF1 can be up-regulated in bronchial epithelial Calu-3 cells by a peptide-nucleic acid (PNA) targeting miR-335-5p, predicted to bind to the 3′-UTR sequence of the NHERF1 mRNA. Treatment of Calu-3 cells with this PNA (R8-PNA-a335) causes also up-regulation of CFTR. (4) Conclusions: We propose miR-335-5p targeting as a strategy to increase CFTR. While the efficiency of PNA-based targeting of miR-335-5p should be verified as a therapeutic strategy in CF caused by stop-codon mutation of the CFTR gene, this approach might give appreciable results in CF cells carrying other mutations impairing the processing or stability of CFTR protein, supporting its application in personalized therapy for precision medicine.

Pulmonary infection secondary to Blastobotrys raffinosifermentans in a cystic fibrosis patient: Review of the literature

Mycoses ◽  
2021 ◽  
Author(s):  
Mohanad Al‐Obaidi ◽  
Hamid Badali ◽  
Connie Cañete‐Gibas ◽  
Hoja P. Patterson ◽  
Nathan P. Wiederhold
Keyword(s):  
Cystic Fibrosis ◽  
Cystic Fibrosis Patient ◽  
Pulmonary Infection ◽  
Review Of The Literature

scholarly journals High lysosomal activities in cystic fibrosis tracheal gland cells corrected by adenovirus-mediated CFTR gene transfer

1999 ◽  
Vol 1453 (1) ◽  
pp. 14-22 ◽  
Author(s):  
W. Kammouni ◽  
D. Naı̈mi ◽  
W. Renaud ◽  
N. Bianco ◽  
C. Figarella ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Gene Transfer ◽  
Cftr Gene ◽  
Gland Cells

A Frequent Large Rearrangement in the CFTR Gene in Cystic Fibrosis Patients from Reunion Island

2006 ◽  
Vol 10 (3) ◽  
pp. 208-214 ◽  
Author(s):  
Juliette Nectoux ◽  
Marie Pierre Audrezet ◽  
Marion Viel ◽  
Chrystel Leroy ◽  
Odile Raguenes ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Cftr Gene ◽  
Reunion Island ◽  
Large Rearrangement ◽  
Réunion Island

scholarly journals Unifocal Granuloma of Femur due to Langerhans' Cell Histiocytosis: A Case Report and Review of the Literature

2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
Harpreet Singh ◽  
Satnam Kaur ◽  
P. Yuvarajan ◽  
Nishant Jain ◽  
Lalit Maini
Keyword(s):  
Case Report ◽  
Clinical Data ◽  
Case History ◽  
Langerhans Cell Histiocytosis ◽  
Eosinophilic Granuloma ◽  
Pediatric Population ◽  
Langerhans Cell ◽  
Long Bones ◽  
Review Of The Literature ◽  
Osteolytic Lesions

The radiological diagnosis of osteolytic lesions of the long bones in pediatric population constitutes a challenge when the case history and clinical data are uncharacteristic. We believe that the description of few clinically and histologically proven cases to verify the existence of radiological signs useful for diagnosis may be of interest. Here, we describe a case of Langerhans' cell histiocytosis (LCH) presenting as unifocal eosinophilic granuloma of femur along with a brief review of the literature.

Complete CFTR gene sequencing in 5,058 individuals with cystic fibrosis informs variant-specific treatment

2021 ◽  
Author(s):  
Karen S Raraigh ◽  
Melis A Aksit ◽  
Kurt Hetrick ◽  
Rhonda G Pace ◽  
Hua Ling ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Specific Treatment ◽  
Gene Sequencing ◽  
Cftr Gene

Clinical and genetic characteristics of rare pathogenic variants of the CFTR gene in Russian patients with cystic fibrosis

2021 ◽  
Vol 31 (2) ◽  
pp. 148-158
Author(s):  
A. Yu. Voronkova ◽  
Yu. L. Melyanovskaya ◽  
N. V. Petrova ◽  
T. A. Adyan ◽  
E. K. Zhekaite ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Variants ◽  
Pancreatic Insufficiency ◽  
Protein Energy Malnutrition ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Cftr Gene ◽  
Genetic Characteristics ◽  
Missense Variants ◽  
Pathogenic Variants

The variety of clinical manifestations of cystic fibrosis is driven by the diversity of the CFTR gene nucleotide sequence. Descriptions of the clinical manifestations in patients with the newly identified genetic variants are of particular interest.The aim of this study was to describe clinical manifestations of the disease with the newly identified genetic variants.Methods. Data from Registry of patients with cystic fibrosis in the Russian Federation (2018) were used. The data review included three steps — the search for frequent mutations, Sanger sequencing, and the search for extensive rearrangements by MLPA. 38 pathogenic variants were identified that were not previously described in the international CFTR2 database. We selected and analyzed full case histories of 15 patients with 10 of those 38 pathogenic variants: p.Tyr84*, G1047S, 3321delG, c.583delC, CFTRdele13,14del18, CFTRdele19-22, c.2619+1G>A, c.743+2T>A, p.Glu1433Gly, and CFTRdel4-8del10-11.Results. A nonsense variant p.Tyr84* was found in 5 patients (0.08 %). Two missense variants c.3139G>A were found in 2 siblings (0.03 %). The c.4298A>G was found in 1 patient. Other variants were detected in a single patient (0.02 %) each. They included two variants of a deletion with a shift of the reading frame 3321delG and c.583delC, two splicing disorders c.2619+1G>A and c.743+2T>A, three extended rearrangements CFTRdele19-22, CFTRdele13,14del18, and CFTRdel4-8del10-11. The last two variants include 2 rearrangements on one allele, which cause the severe course in two young children. 8 of the 10 variants are accompanied by pancreatic insufficiency (PI). Among patients with p.Tyr84*, one had ABPA, one had liver transplantation, and all had Pseudomonas aeruginosa infection. Nasal polyps were diagnosed in 2 patients with p.Tyr84*, 1 with G1047S, 1 with CFTRdel4-8del10-11, and 1 patient with 3321delG, who also had osteoporosis and cystic fibrosis-related diabetes (CFRD). 2 patients with PI with 3321delG and CFTRdel4-8del10-11 genetic variants, and 1 with PI with p.Glu1433Gly genetic variant had severe protein-energy malnutrition (PEM).Conclusion. Clinical manifestations of previously undescribed CFTR genetic variants were described. 5/10 genetic variants should be attributed to class I, 3/10 – to class 7 of the function classification of pathogenic CFTR gene variants associated with transcription and translation disruptions. Class of the identified missense variants c.3139G>A and c.4298A>G has not been established and requires further functional, cultural, and molecular genetic studies.

Identification of two novel mutations (296 + 1G − C and A46D) in exon 2 of the CFTR gene in Greek cystic fibrosis patients

1995 ◽  
Vol 9 (4) ◽  
pp. 283-285
Author(s):  
Maria Tzetis ◽  
Emmanuel Kanavakis ◽  
Thalia Antoniadi ◽  
Joanne Traeger-Synodinos ◽  
Stavros Doudounakis ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Cftr Gene ◽  
Novel Mutations ◽  
Exon 2
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