Futoshi Kuribayashi
   Department     ,
Article types 原著
Language English
Peer review Peer reviewed
Title Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB
Journal Formal name:Journal of medical genetics
Abbreviation:J. Med. Genet.
Volume, Issue, Page 48(3),205-209頁
Author and coauthor Takeshi Tanaka, Natsuki Motoi, Yoshiko Tsuchihashi, Ryushi Tazawa, Chinatsu Kaneko, Takahito Nei, Toshiyuki Yamamoto, Tomayoshi Hayashi4, Tsutomu Tagawa, Takeshi Nagayasu, Futoshi Kuribayashi, Koya Ariyoshi, Koh Nakata, and Konosuke Morimoto
Publication date 2011/03
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.