Cystic Fibrosis Patients Susceptible To Chronic Respiratory Infection Due To Gene Mutation
Researchers at the University of WashingtonÂ have madeÂ 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 inÂ DCTN4 gene.
Cystic fibrosis isÂ 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 CFTRÂ protein. CFTRÂ (cystic fibrosis transmembrane conductance regulator) causes an abnormality in chloride and sodium transportation through the epithelium. The result of this anomaly lies in the viscousÂ secretions ofÂ the exocrine glands. Therefore, patients suffering from cystic fibrosis often haveÂ COPDÂ (chronic obstructive pulmonary disease)Â and exocrine pancreatic insufficiency. Also, patientsÂ suffer fromÂ respiratory infections with Pseudomonas aeruginosa, a rod-shaped, Gram-negative bacterium. Usually, this bacteria affects mainlyÂ immunodeprived patients. Chronic infectionsÂ 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. DCTN4Â gene encodes dynactinÂ 4, a protein with bacterial clearance role. Researchers found that cystic fibrosis patients who were susceptible to infectionÂ had at least one mutation in theÂ DCTN4 gene.
This discovery was made by sequential DNA analysis of 91 patients, namely by exomeÂ sequencing. Mary J. Emond, the lead author of the report published July 8 in Nature Genetics, said that they did not seek this particular geneÂ during theirÂ study. This gene was detected after the statistical analysis of data collected from the 91 patients. Of the 91, a number ofÂ 43 patients wereÂ suffering fromÂ early respiratory infections, unlike the other 48Â who haveÂ not yet developed anyÂ chronic respiratory infection. Subsequently, researchers examined data comparing results with another group of 1322 participants.
CysticÂ fibrosis is one of the most common genetic syndromes that reduce life expectancyÂ in whites. This disease is characterized byÂ abnormal exocrine gland secretionÂ inÂ the entire body. Earliest sign is meconiumÂ ileus, which is due to the obstruction of ileum due to viscousÂ meconium.Â There is also a chronic bronchial obstruction that not only cause frequent respiratory infections but also damage theÂ pulmonary circulation and causes right ventricular hypertrophy. Exocrine pancreatic insufficiency leads to steatorrhea stools, that is fattyÂ stools.Â Â Cystic fibrosis isÂ not a curableÂ disease, treatment is only symptomatic.