Cystic Fibrosis Patients Susceptible To Chronic Respiratory Infection Due To Gene Mutation
Researchers at the University of Washington have made new findings on cystic fibrosis. The survey, published July 8 in Nature Genetics, points out that cystic fibrosis patients are more susceptible to chronic respiratory infections due to mutations in DCTN4 gene.
Cystic fibrosis is a congenital disease caused by mutation of a gene located on long arm of chromosome 7. The most common mutation, F508, leads to the absence of a phenylalanine residue in position 508 of CFTR protein. CFTR (cystic fibrosis transmembrane conductance regulator) causes an abnormality in chloride and sodium transportation through the epithelium. The result of this anomaly lies in the viscous secretions of the exocrine glands. Therefore, patients suffering from cystic fibrosis often have COPD (chronic obstructive pulmonary disease) and exocrine pancreatic insufficiency. Also, patients suffer from respiratory infections with Pseudomonas aeruginosa, a rod-shaped, Gram-negative bacterium. Usually, this bacteria affects mainly immunodeprived patients. Chronic infections during cystic fibrosis patients is associated with poor quality of life and even with low life expectancy.
Recently, researchers found that patients with cystic fibrosis who are more susceptible to infection with Pseudomonas have a mutation in a gene called DCTN4. DCTN4 gene encodes dynactin 4, a protein with bacterial clearance role. Researchers found that cystic fibrosis patients who were susceptible to infection had at least one mutation in the DCTN4 gene.
This discovery was made by sequential DNA analysis of 91 patients, namely by exome sequencing. Mary J. Emond, the lead author of the report published July 8 in Nature Genetics, said that they did not seek this particular gene during their study. This gene was detected after the statistical analysis of data collected from the 91 patients. Of the 91, a number of 43 patients were suffering from early respiratory infections, unlike the other 48 who have not yet developed any chronic respiratory infection. Subsequently, researchers examined data comparing results with another group of 1322 participants.
Cystic fibrosis is one of the most common genetic syndromes that reduce life expectancy in whites. This disease is characterized by abnormal exocrine gland secretion in the entire body. Earliest sign is meconium ileus, which is due to the obstruction of ileum due to viscous meconium. There is also a chronic bronchial obstruction that not only cause frequent respiratory infections but also damage the pulmonary circulation and causes right ventricular hypertrophy. Exocrine pancreatic insufficiency leads to steatorrhea stools, that is fatty stools. Cystic fibrosis is not a curable disease, treatment is only symptomatic.