Pulmonary Fibrosis Syndrome via the SFTPA2 Gene

Pulmonary fibrosis (PF) is a chronic progressive lung disease caused by lung scarring. When the scar forms, the lung tissue becomes thicker and loses 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 individuals to develop pulmonary fibrosis (Wolters et 2014). Linkage analysis studies have identified multiple genes including SFTPA2, which are involved in the inherited form of IPF (Kropski et al. 2013).

Pathogenic variants in SFTPA2 cause idiopathic pulmonary fibrosis and inherited in autosomal dominant manner. The SFTPA2 gene located at chromosome 10q22.3 spreads over 8 kb of genomic DNA and encodes surfactant protein A2, an isoform of surfactant protein. The pathogenic variants in SFTPA2 could result in surfactant protein A2 being misfolded and accumulated in Endoplasmic reticulum (ER), which lead to ER stress and dysfunction of the alveolar type II cells (Wang et al. 2009). So far, only missense pathogenic variants have been reported and no large deletions or duplications have been documented for the SFTPA2 gene (Human Gene Mutation Databases).

Pathogenic SFTPA2 variants appear to be a rare cause of pulmonary fibrosis and cause less than 1% of familial pulmonary fibrosis cases (Talbert and Schwartz 2015).

SFTPA2 is located on chromosome 10q22.3. Testing involves PCR amplification from genomic DNA and bidirectional Sanger sequencing of the coding exons and ~10 bp of adjacent noncoding sequences. We will also sequence any single exon (Test #100) in family members of patients with a known pathogenic variant or to confirm research results.