Pulmonary Fibrosis and Surfactant Dysfunction Disorders Panel

Pulmonary fibrosis (PF) is a chronic progressive lung disease caused by lung scarring. When the scar forms, the lung tissue becomes thicker and losses its ability to transfer oxygen into the bloodstream. The severity and natural course of pulmonary fibrosis varies from person to person. Symptoms of pulmonary fibrosis include shortness of breath, dry cough, weight loss and fatigue. The etiology of pulmonary fibrosis is varied and most cases of pulmonary fibrosis have no known cause called idiopathic pulmonary fibrosis (IPF). It is estimated that the prevalence of IPF is 50 per 100,000 (Raghu et al. 2006). Pulmonary fibrosis also occurs in families, suggesting genetic factors predispose some individuals to develop pulmonary fibrosis (Wolters et 2014).

Pulmonary surfactant generated by type II alveolar epithelial cells is a mixture of phospholipids and proteins. Surfactant dysfunction disorders can be caused by pathogenic variants in genes critical for the production and function of pulmonary surfactant. The clinical presentations of surfactant dysfunction range from neonatal respiratory failure to interstitial lung disease. These disorders can be familial or sporadic cases (Gower et al. 2011).

Pulmonary fibrosis and surfactant dysfunction disorders are a group of genetically heterogeneous disorders caused by various interactions between genetic components and environmental exposures. Familial inheritance can be autosomal dominant (AD), autosomal recessive (AR), and sex-chromosome linked. The ELMOD2, NKX2-1, SFTPA1, SFTPA2, SFTPC, and TERC genes are associated with autosomal dominant pulmonary disorders. The ABCA3, CSF2RB, SFTPB and SFTPD genes are associated with autosomal recessive disorders. The TERT gene is associated both autosomal dominant and recessive disorders. See individual gene test descriptions for information on molecular biology of gene products.

This test should detect causative variants in ~20% of familial pulmonary fibrosis patients (Diaz de Leon et al. 2011; Garcia et al. 2011; van Moorsel et al. 2010).

There are only a few isolated cases reported for large deletions/duplications involving ABCA3, NKX2-1, SFTPB, SFTPC and TERCT. The clinical sensitivity is therefore predicted to be low.

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).