Their study, “Next-generation sequencing for identifying genetic mutations in adults with bronchiectasis,” was published in the Journal of Thoracic Disease.
Bronchiectasis is characterized by the enlargement, damage, and scarring of the bronchi — the breathing structures of the lungs — due to defects in the airway defense mechanisms.
These include increased mucus production and damage to the tiny hairs (cilia) that line the inside of the airways, leading to a buildup of mucus which promotes bacteria growth.
Whether genetic mutations underlie bronchiectasis remains unknown, although early evidence suggests that mutations in certain genes, such as the CFTR gene, may be implicated in the disease. The CFTR gene provides instructions to make a protein that regulates mucus production in the lungs and other organs. Mutations in this gene are the cause of cystic fibrosis.
Genetic mutations related to primary ciliary dyskinesia (defects in promoting cilia movement in the airways and other organs) and defects in the immune system (immunodeficiency) may also promote bronchiectasis.
Researchers used a valuable genomic tool called next-generation sequencing to identify genetic mutations implicated in bronchiectasis. With this technique they can “read” the DNA code with high sensitivity and accuracy many times and detect potential errors (mutations) in genes that may underlie diseases.
They performed a genetic screen in blood samples from 192 bronchiectasis patients and 100 healthy controls. The screening focused on 32 genes that have been linked to cystic fibrosis and other lung diseases and so were likely candidates to have a role in bronchiectasis, too.
The analysis identified 162 genetic alterations (due to their low frequency they are called rare variants) in bronchiectasis patients and 85 in control subjects.
In bronchiectasis patients, 25 rare variants were associated with the cystic fibrosis-causing CFTR gene. Additionally, researchers identified 117 variants associated with another protein channel linked to cystic fibrosis, the epithelial sodium channel (ENaC), and 18 variants associated with primary ciliary dyskinesia.
Researchers then looked closely into the gene variants in the CFTR gene and three other genes linked to cystic fibrosis, called SCNN1A, SCNN1B and SCNN1G.
Forty-three patients with bronchiectasis carried 15 CFTR gene variants, while 25 healthy controls had 13 CFTR gene variants. Mutations in the SCNN1A and SCNN1B genes were detected in six bronchiectasis patients, but only in one control.
A total of 117 rare variants linked to primary ciliary dyskinesia-associated genes were found in 101 bronchiectasis patients.
Bronchiectasis patients with mutations in the two copies of a gene linked to the primary ciliary dyskinesia called DNAH11 had more severe disease. The same pattern of increased severity was detected in patients carrying rare variants affecting the two copies of the DNAH5 and CFTR gene.
Overall, the team concluded that “genetic mutations leading to impaired host defense might [be] implicated in the pathogenesis of bronchiectasis,” namely mutations in both copies of genes associated with CF and primary ciliary dyskinesia.
However, the researchers noted that others causes cannot be excluded. “Our findings cannot address whether other pathways (e.g., immunodeficiency, airway inflammation) are associated with bronchiectasis,” they wrote.
According to the team, “genetic screening may be a useful tool for unraveling the underlying causes of bronchiectasis.”