In addition to the histological phenotype, subcategories of interstitial lung diseases may be defined genetically. Cases with a strong genetic indication are analyzed using Whole Exome Trio Analysis (parallel analysis and interpretation with the genetic information of healthy parents). Aim of the study is the identification of the disease-causing variant to define novel candidate genes causing the specific phenotype. Reduction of invasive diagnostic procedure in the future is desirable.

The ATP-binding cassette (ABC) transporter ABCA3 is a phospholipid transporter, which is implicated in pulmonary surfactant homeostasis and localized at the limiting membrane of lamellar bodies, the storage compartment for surfactant in alveolar type II cells. Pulmonary surfactant, a complex mixture of lipids and proteins that lines the alveolar surface, prevents alveolar collapse by reducing the surface tension at the air-liquid interface in the alveoli. Mutations in ABCA3 were identified as the most common monogenetic cause of surfactant dysfunction disorders in newborns and interstitial lung diseases in children and young adults.

Although the effect of mutations resulting in truncated or incomplete proteins can be predicted, the consequences of missense variants cannot be as easily. Therefore, we investigate the intracellular handling and disturbance of the cellular surfactant system of clinically relevant ABCA3 missense mutations..