Filamin A Mutations

Emphysema is a chronic respiratory disorder characterized by destruction of alveoli, usually due to cigarette smoking or exposure to noxious particles or gases. Dysfunction of proteins that are involved in lung development and maintenance, such as alpha-1 antitrypsin, also contributes to emphysema. Filamin A (FLNA) is an actin-binding protein involved in cytoskeleton reorganization. Mutations in the FLNA gene classically lead to abnormal neuronal migration and connective and vascular tissue anomalies. Pulmonary manifestations consist of a wide range of pulmonary disorders that occur during infancy. We report the first familial case of emphysema in non- and very low-smoking adults who carry a loss-of-function mutation of the FLNA gene. The identification of this new risk factor for emphysema encourages (1) screening, prevention and monitoring of pulmonary disorders in patients with FLNA mutation and (2) screening for FLNA mutation in patients with early-onset emphysema that is associated with low-smoking or vascular or connective tissue anomalies.