Cystic fibrosis transmembrane conductance regulator CFTR gene

Cystic fibrosis is an autosomal recessive disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene producing a dysfunctional chloride channel, normally located on the apical membrane of exocrine glands [16]. The disease manifests itself at an early age in the lung with accumulation of thick, sticky mucus and bacterial infections. These infections are followed by an inflammatory response, resulting in an infiltration of neutrophils... 

Recombinant adenoviruses have been used to deliver the cystic fibrosis transmembrane conductance regulator (CFTR) gene to the lungs of patients with cystic fibrosis. Adenoviruses are ideal for this approach because they naturally infect human respiratory cells. In these adenoviral vectors, the CFTR gene has been put in place of the adenovirus El A gene. The viral vectors can be packaged in a specialized human cell line that expresses El A protein to complement El A deletion in the viral genome. 

Zielenski, J., Rozmahel, R., Bozon, D., Kerem, B. S., Grelczack, Z., Riordan, J. R., Rommens, J, and Tsui, L. C. (1991) Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene Genomics 10,214-228. 

Viral vectors have obvious advantages, particularly their ease of tissue penetration and their specific tissue tropism. Their chief disadvantage is the potential for inflammatory and antibody responses (Wilson, 1995, 1996 Adesanya et ah, 1996 Engelhard et al., 1994 Yang et al, 1994). For example, viral-induced inflammation is dose-limiting for therapy with the cystic fibrosis transmembrane conductance regulator (CFTR) gene (Wilson, 1995) in an adenoviral vector, which is the most extensively-studied construct so far. 

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been described in ABPA patients without clinical evidence of cystic fibrosis. Gene mutations may play an etiologic role in a subset of the patients with ABPA (72). 

The gene product is termed cystic fibrosis transmembrane conductance regulator (CFTR), and it codes for a chloride ion channel. It may also carry out additional (as yet undetermined) functions. 

CF is caused by the absence of a protein called cystic fibrosis transmembrane conductance regulator (CFTR). This protein is required for the transport of chloride ions across cell membranes. On the molecular level, there is a mutation in the gene that encodes for CFTR. As a result, CFTR cannot be processed properly by the cell and is unable to reach the exocrine glands to assume its transport function. 

The gene responsible for CF codes for the cystic fibrosis transmembrane conductance regulator (CFTR), which is a chloride channel expressed on the surface of epithelial cells that line the affected organs. 

The cystic fibrosis (c/) gene was first identified in 1989. It codes for a 170 kDa protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which serves as a chloride channel in epithelial cells. Inheritance of a mutant cftr gene from both parents results in the CF phenotype. While various organs are affected, the most severely affected are the respiratory epithelial cells, which have, unsurprisingly, become the focus of attempts at corrective gene therapy. 

Cystic fibrosis is the most common lethal autosomal recessive disease affecting the Caucasian population. It has a frequency of approximately 1 in 2500 and a carrier frequency of approximately 1 in 25. The protein affected is the cystic fibrosis transmembrane conductance regulator (CFTR), which is a chloride ion channel. There are over 1000 mutations that have been discovered in the CFTR gene and over 80 percent of these mutations lead to disease. The mutations lead to (1) defective or decreased protein production, (2) defective processing of the protein, (3) protein that is defective in the regulation of the chloride channel, or (4) defect in the transport of chloride ions. The most common mutation, a deletion of a phenylalanine residue at amino acid position 508 (AFjog), results in misfolding of the protein it consequently does not traffic to the membrane. 

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