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


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Title: Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB.
Authors: Tanaka, Takeshi / Motoi, Natsuki / Tsuchihashi, Yoshiko / Tazawa, Ryushi / Kaneko, Chinatsu / Nei, Takahito / Yamamoto, Toshiyuki / Hayashi, Tomayoshi / Tagawa, Tsutomu / Nagayasu, Takeshi / Kuribayashi, Futoshi / Ariyoshi, Koya / Nakata, Koh / Morimoto, Konosuke
Issue Date: Mar-2011
Publisher: BMJ Publishing
Citation: Journal of medical genetics, 48(3), pp.205-209; 2011
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-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.
URI: http://hdl.handle.net/10069/24550
ISSN: 00222593
DOI: 10.1136/jmg.2010.082586
PubMed ID: 21075760
Rights: Copyright Article author (or their employer) 2010.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/24550

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