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

Article Details


Tanaka T, Motoi N, Tsuchihashi Y, Tazawa R, Kaneko C, Nei T, Yamamoto T, Hayashi T, Tagawa T, Nagayasu T, Kuribayashi F, Ariyoshi K, Nakata K, Morimoto K

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

J Med Genet. 2011 Mar;48(3):205-9. doi: 10.1136/jmg.2010.082586. Epub 2010 Nov 12.

PubMed ID
21075760 [ View in PubMed

BACKGROUND: Disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signalling causes pulmonary alveolar proteinosis (PAP). Rarely, genetic defects in neonatal or infant-onset PAP have been identified in CSF2RA. However, no report has clearly identified any function-associated genetic defect in CSF2RB. METHODS AND RESULTS: The patient was diagnosed with PAP at the age of 36 and developed respiratory failure. She was negative for GM-CSF autoantibody and had no underlying disease. Signalling and genetic defects in GM-CSF receptor were screened. GM-CSF-stimulated STAT5 phosphorylation was not observed and GM-CSF-Rbetac expression was defective in the patient's blood cells. Genetic screening revealed a homozygous, single-base deletion at nt 631 in exon 6 of CSF2RB on chromosome 22, which caused reductions in GM-CSF dependent signalling and function. Both parents, who were second cousins, showed no pulmonary symptoms, and had normal GM-CSF-signalling, but had a CSF2RB allele with the identical deletion, indicating that the mutant allele may give rise to PAP in an autosomal recessive manner. CONCLUSIONS: This is the first report identifying a genetic defect in CSF2RB that causes deficiency of GM-CSF-Rbetac expression and impaired signalling downstream. These results suggested that GM-CSF signalling was compensated by other signalling pathways, leading to adult-onset PAP.

DrugBank Data that Cites this Article

NameUniProt ID
Cytokine receptor common subunit betaP32927Details