RT Journal Article SR Electronic T1 Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 205 OP 209 DO 10.1136/jmg.2010.082586 VO 48 IS 3 A1 Tanaka, Takeshi A1 Motoi, Natsuki A1 Tsuchihashi, Yoshiko A1 Tazawa, Ryushi A1 Kaneko, Chinatsu A1 Nei, Takahito A1 Yamamoto, Toshiyuki A1 Hayashi, Tomayoshi A1 Tagawa, Tsutomu A1 Nagayasu, Takeshi A1 Kuribayashi, Futoshi A1 Ariyoshi, Koya A1 Nakata, Koh A1 Morimoto, Konosuke YR 2011 UL http://jmg.bmj.com/content/48/3/205.abstract AB 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.