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http://purl.uniprot.org/citations/21075760http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21075760http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21075760http://www.w3.org/2000/01/rdf-schema#comment"

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-Rβc 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-Rβc expression and impaired signalling downstream. These results suggested that GM-CSF signalling was compensated by other signalling pathways, leading to adult-onset PAP."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.org/dc/terms/identifier"doi:10.1136/jmg.2010.082586"xsd:string
http://purl.uniprot.org/citations/21075760http://purl.org/dc/terms/identifier"doi:10.1136/jmg.2010.082586"xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Hayashi T."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Hayashi T."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Tanaka T."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Tanaka T."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Yamamoto T."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Yamamoto T."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Tagawa T."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Tagawa T."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Morimoto K."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Morimoto K."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Tsuchihashi Y."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Tsuchihashi Y."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Nakata K."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Nakata K."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Kaneko C."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Kaneko C."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Ariyoshi K."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Ariyoshi K."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Kuribayashi F."xsd:string
http://purl.uniprot.org/citations/21075760http://purl.uniprot.org/core/author"Kuribayashi F."xsd:string
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