Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1.
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Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is usually caused by neutralizing autoantibodies to GM-CSF or is secondary to other underlying diseases. Rarely, genetic defects in surfactant proteins or the common beta chain for the GM-CSF receptor (GM-CSFR) are causal. Using a combination of cellular, molecular, and genomic approaches, we provide the first evidence that PAP can result from a genetic deficiency of the GM-CSFR alpha chain, encoded in the X-chromosome pseudoautosomal region 1.
author list (cited authors)
Martinez-Moczygemba, M., Doan, M. L., Elidemir, O., Fan, L. L., Cheung, S. W., Lei, J. T., ... Huston, D. P.
complete list of authors
Martinez-Moczygemba, Margarita||Doan, Minh L||Elidemir, Okan||Fan, Leland L||Cheung, Sau Wai||Lei, Jonathan T||Moore, James P||Tavana, Ghamartaj||Lewis, Lora R||Zhu, Yiming||Muzny, Donna M||Gibbs, Richard A||Huston, David P