جستجوی مقالات مرتبط با کلیدواژه « CFTR gene » در نشریات گروه « پزشکی »

Cystic fibrosis (CF) is known as one of the most common autosomal recessive disorders, which is caused by mucosal glands. A deficiency in the Cystic fibrosis transmembrane conductance regulator gene (CFTR), which encodes a chloride channel, triggers damage to epithelial cells in respiratory ducts, pancreas, intestine, genital ducts in males, liver system, and sweat glands.

This study aimed to conduct the sequencing of 27 exons of the CFTR gene to screen the spectrum of the variants in patients from all over Iran from different ethnicities.

This study is a descriptive-analytical, that was performed for eleven years from 2010 to 2021. Totally 345 patients were referred to Tehran Medical Genetics Laboratory by specialists. These patients were categorized into four groups. The first group included clinically confirmed patients of CF having clinical features and biochemical abnormalities, plus a positive sweat chloride test. The second group included couples with an alive or deceased child affected. The third group included CBAVD (Congenital bilateral absence of the vas deferens) cases, and the fourth group included prenatal diagnoses who were looking for carrier detection, or her spouse is affected with CBAVD.

Fifty-four variants and five deletions were found from 345 patients, the most common frequent variant were c.1521_1523delCTT ([delta]F508) (47 (6.81%)), c.1000C>T (R334W, 31 (4.45%)), c.1911delG (2043delG, 25 (3.62%)), c.2051_2052delAAinsG (2183AA->G, 15 (2.17%)), c.1624G>T (G542X, 12 (1.74%)), c.1697C>A (A566D, 12 (1.74%)), c.1210-12T [5] (9(1.30%)) and c.3196C>T (R1066C,7 (1.01%)) respectively and frequency of other variants were less than 1%. Deletion in some exons was established by MLPA assay, the most common deletion was c. (53+1_54-1) _ (164+1_165-1) del (CFTRdele2, 7 (1.01%)).

This study improves our knowledge concerning carrier analysis and genetic counseling. Also, it helps to develop a cost-effective newborn screening program.

Cystic fibrosis (CF) is an inherited autosomal recessive disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The present study aimed to investigate the genetic modification of CF with ΔF508 mutation of the CFTR gene using CRISPR in peripheral blood mononuclear cells (PBMCs).

Two single guide RNAs were designed to target sequences in the CFTR gene. The transfection efficiency of PBMC cells was examined through evaluation of green fluorescent protein (GFP) expression using fluorescent microscopy. Moreover, a sgRNA-Cas9 plasmid was tested to target the CFTR gene. The ΔF508 gene modification was evaluated and confirmed by PCR and Sanger sequencing methods.

Our results indicate the feasibility of site-specific gene targeting with the CRISPR/Cas9 system. 33% of the samples were corrected using CRISPR in mutant locus and confirmed by sequence blast at NCBI databases and primers outside the arm locus. CRISPR/Cas9 approach represents an efficient tool to repair the ΔF508 mutation of the CFTR gene in PBMC Cells.

Therefore, the CRISPR system can be highly efficient and specific and provides a powerful approach for genetic engineering of cells and model animals. Generally, the proposed method opens new insights into the treatment of human diseases.

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in CFTR genes that affect chloride ion channel. The CF is a good nominee for gene therapy as the asymptomatic carriers are phenotypically normal, and the desired cells are accessible for vector delivery. Gene therapy shows promising effects involving the correction of gene or replacement of the mutant gene with the functional one. Accordingly, various viral and non-viral carriers have been investigated. Although viral vectors are efficient, they have some problems, including mutagenesis, host immune response, higher toxicity, and costliness. On the other hand, non-viral vectors have less toxicity and immunogenic response and are easier to prepare. For a successful gene therapy, the cargo must be delivered to the target site. However, various barriers are faced by non-viral vectors, which make the gene delivery to the target site difficult. Extracellular barrier, which is the first barrier, include nucleases, negatively charged serum proteins, blood cells, and activated immune system. Ciliated epithelium, mucus gel, apical surface glycocalyx, and plasma membrane come in the second category of the barriers. Furthermore, the third category, which is related to the intracellular barriers, includes endosome and lysosome, cytoplasmic nucleases, viscous environment of cytoplasm with different proteins, and finally nuclear membrane. Various approaches have been proposed to increase the systematic delivery of vectors and enhance their efficiency. Some of these approaches include surface coating with inert polymers, modification of surface charge with anionic polymers, and enhancement of endocytosis and reduction of toxicity by using polyethylene glycol. This review paper was conduct to highlight the barriers faced by non-viral vectors when carrying a genetic payload to the lungs. This study also involved the investigation of the strategies and different types of modifications targeted toward the improvement of the efficiency of non-viral vectors.

Cystic fibrosis (CF) is one of the most common autosomal recessive disorders in Caucasian population. The incidence of disorder varies among different religious, ethnic and geographical isolates. The aim of this study was to identify the spectrum and the frequency of known and unknown disease-causing mutations in Iranian CF patients.
Genomic DNA was extracted from peripheral whole blood with a QI-Aamp DNA Mini-Kit. Mutation analysis was done in the CFTR gene including complete coding region and intron/exon boundaries using a direct sequencing method.
In general, ten mutations were identified in 27 CF cases. Two out of 10 mutations, 754delT and GGTGGCdel/TTGins, were reported as novel mutations. The most common observed mutations in patients were R334W (40.74%), ΔF508 (18.5%), K710X (12.96%) and D110H (5.5%), 1897C>G (1.85%), R1162X (1.85%), S466X (1.85%) and T1036I (1.85%).
The finding indicated a unique mutation panel which can be used in genetic counseling, prenatal diagnosis and future screening of CF in Iran. Although ΔF508 is the most common mutation in other populations including Caucasian, this mutation seem not to have an important role in Iranian CF patients. Findings suggest that a different approach in molecular genetics diagnostic strategies in Middle Eastern countries including Iran should be considered.