PT  - JOURNAL ARTICLE
AU  - Tanaka, Takeshi
AU  - Motoi, Natsuki
AU  - Tsuchihashi, Yoshiko
AU  - Tazawa, Ryushi
AU  - Kaneko, Chinatsu
AU  - Nei, Takahito
AU  - Yamamoto, Toshiyuki
AU  - Hayashi, Tomayoshi
AU  - Tagawa, Tsutomu
AU  - Nagayasu, Takeshi
AU  - Kuribayashi, Futoshi
AU  - Ariyoshi, Koya
AU  - Nakata, Koh
AU  - Morimoto, Konosuke
TI  - Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in <em>CSF2RB</em>
AID  - 10.1136/jmg.2010.082586
DP  - 2011 Mar 01
TA  - Journal of Medical Genetics
PG  - 205--209
VI  - 48
IP  - 3
4099  - http://jmg.bmj.com/content/48/3/205.short
4100  - http://jmg.bmj.com/content/48/3/205.full
SO  - J Med Genet2011 Mar 01; 48
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.