Genetics in pulmonary fibrosis--familial cases provide clues to the pathogenesis of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most common form of the idiopathic interstitial pneumonias and remains a disease with a poor prognosis. Familial interstitial pneumonia (FIP) occurs when 2 or more individuals from a given family have an idiopathic interstitial pneumonia. FIP cases have been linked to mutations in surfactant protein C, surfactant protein A2, telomerase reverse transcriptase and telomerase RNA component. Together, mutations in these 4 genes likely explain only 15% to 20% of FIP cases and are even less frequent in sporadic IPF. However, dysfunctional aspects of the pathways that are involved with these genes are present in sporadic forms of IPF even in the absence of mutations, suggesting common underlying disease mechanisms. By serving as a resource for identifying the current and future genetic links to disease, FIP families hold great promise in defining IPF pathogenesis, potentially suggesting targets for the development of future therapies.