{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:37:35Z","timestamp":1790534255372,"version":"4.1.0"},"reference-count":19,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2010,10,1]]},"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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 <jats:italic>CSF2RA<\/jats:italic>. However, no report has clearly identified any function-associated genetic defect in <jats:italic>CSF2RB<\/jats:italic>.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>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-R\u03b2c expression was defective in the patient's blood cells. Genetic screening revealed a homozygous, single-base deletion at nt 631 in exon 6 of <jats:italic>CSF2RB<\/jats:italic> 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 <jats:italic>CSF2RB<\/jats:italic> allele with the identical deletion, indicating that the mutant allele may give rise to PAP in an autosomal recessive manner.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This is the first report identifying a genetic defect in <jats:italic>CSF2RB<\/jats:italic> that causes deficiency of GM-CSF-R\u03b2c expression and impaired signalling downstream. These results suggested that GM-CSF signalling was compensated by other signalling pathways, leading to adult-onset PAP.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2010.082586","type":"journal-article","created":{"date-parts":[[2010,11,12]],"date-time":"2010-11-12T23:39:18Z","timestamp":1289605158000},"page":"205-209","source":"Crossref","is-referenced-by-count":94,"title":["Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in <i>CSF2RB<\/i>"],"prefix":"10.1136","volume":"48","author":[{"given":"Takeshi","family":"Tanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuki","family":"Motoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Tsuchihashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryushi","family":"Tazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinatsu","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahito","family":"Nei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomayoshi","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Tagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Nagayasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futoshi","family":"Kuribayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koya","family":"Ariyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koh","family":"Nakata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konosuke","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2010,11,12]]},"reference":[{"key":"2025101721433198000_48.3.205.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023226"},{"key":"2025101721433198000_48.3.205.2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.6.875"},{"key":"2025101721433198000_48.3.205.3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1565"},{"key":"2025101721433198000_48.3.205.4","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200708-1271OC"},{"key":"2025101721433198000_48.3.205.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.8171324"},{"key":"2025101721433198000_48.3.205.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.21.9565"},{"key":"2025101721433198000_48.3.205.7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080990"},{"key":"2025101721433198000_48.3.205.8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080759"},{"key":"2025101721433198000_48.3.205.9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119758"},{"key":"2025101721433198000_48.3.205.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.02.017"},{"key":"2025101721433198000_48.3.205.11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.050106.093909"},{"key":"2025101721433198000_48.3.205.12","doi-asserted-by":"crossref","unstructured":"Suzuki T Sakagami T Young LR Carey BC Wood RE Luisetti M Wert SE Rubin BK Kevill K Chalk C Whitsett JA Stevens C Nogee LM Campo I Trapnell BC . 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