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