Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB

Disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling causes pulmonary alveolar proteinosis (PAP) characterized by excessive accumulation of surfactant in the lung. To date, adult-onset congenital PAP has not been reported. We found the first adult-onset patient with GM-CSF-Rβc deficiency, diagnosed as PAP pathologically at age 36. She had diminished GM-CSF-dependent signaling and functions in leukocytes and homozygous, one-base deletion in the exon 6 of CSF2RB of chromosome 22, which was inherited in autosomal recessive manner from both parents who were second cousins.The results suggested that GM-CSF signaling was compensated by other factor(s), preventing from development of PAP for many years. (By Dr. Koh Nakata, http://jmg.bmj.com/content/early/2010/11/11/jmg.2010.082586.abstract?papetoc )