ヤマモト　トシユキ   Toshiyuki Yamamoto   山本　俊至    所属   医学部 医学科（東京女子医科大学病院）    職種   教授
論文種別	症例報告
言語種別	英語
査読の有無	査読なし
表題	Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB
掲載誌名	正式名：Journal of Medical Genetics
巻・号・頁	48(3),pp.205-209
著者・共著者	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
発行年月	2011
概要	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