CSF2RB – Hereditary Pulmonary Alveolar Proteinosis

Hereditary pulmonary alveolar proteinosis (PAP) is a rare autosomal recessive disorder characterized by surfactant accumulation and progressive respiratory failure. The association between CSF2RB and PAP is supported by a single adult patient who experienced disease recurrence 9 months after bilateral lung transplantation. Genetic analysis identified a CSF2RB nonsense deletion truncating the receptor β‐chain, and functional assays demonstrated impaired GM‐CSF–mediated signaling in recipient‐derived alveolar macrophages (PMID:27595063).

Limited genetic evidence (one proband, no familial segregation) and case‐level functional data justify a Limited classification under ClinGen criteria. The GM‐CSF receptor signaling defect confirms a loss‐of‐function mechanism, informing diagnostic sequencing and highlighting hematopoietic stem cell transplantation as a targeted therapeutic option. Key Take-home: Genetic testing for CSF2RB in PAP patients can guide transplant strategy and cytotherapy planning.

References

• Respiratory Medicine Case Reports • 2016 • Recurrence of pulmonary alveolar proteinosis after bilateral lung transplantation in a patient with a nonsense mutation in CSF2RB. PMID:27595063

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