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Toshiyuki Yamamoto
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Professor |
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| Article types | Case report |
| Language | English |
| Peer review | Non peer reviewed |
| Title | Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB |
| Journal | Formal name：Journal of Medical Genetics |
| Volume, Issue, Page | 48(3),pp.205-209 |
| Author and coauthor | Takeshi Tanaka, Natsuki Motoi, Yoshiko Tsuchihashi, Ryushi Tazawa, Chinatsu Kaneko, Takahito Nei, Toshiyuki Yamamoto, Tomayoshi Hayashi, Tsutomu Tagawa, Takeshi Nagayasu, Futoshi Kuribayashi, Koya Ariyoshi, Koh Nakata, Konosuke Morimoto |
| Publication date | 2011 |
| Summary | 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. |
| DOI | 10.1136 |