Unravelling the genetic landscape of early-onset emphysema by whole exome sequencing

Emphysema, a pathological hallmark of Chronic Obstructive Pulmonary Disease, is characterized by the enlargement and destruction of alveoli in result of cell death and loss of elastic recoil. Typically, its onset before the fifth decade of life is attributed to alpha1-antitrypsin deficiency, a rare genetic condition. However, premature lung aging as an outcome of dysfunctional telomeres has been proven as another cause for family aggregation of young emphysema cases. Here, we report the findings of an agnostic study of 6 unrelated cases of early-onset emphysema (18-44 years). Whole exome sequencing was done using an Ion S5 XL system (>30x), where reads alignment and variant calling were executed through Ion Report software. Next, a manually curated procedure based in ANNOVAR output was employed to filter rare variants according to frequencies in Europeans (