Biallelic loss-of-function PTPN6 variants lead to inflammatory lung disease and hemolytic anemia.

Biallelic loss-of-function variants in PTPN6 are linked to early-onset anemia and severe inflammatory lung disease, including ARDS, in seven children from five families.

• Why it matters: Understanding genetic causes of inflammatory lung disease can improve diagnosis and treatment options for life-threatening conditions like ARDS, which have limited targeted therapies.
• What they did: Researchers identified causative variants in PTPN6 that destabilize SHP1 and eliminate its phosphatase activity in affected children, highlighting a novel inborn error of immunity.
• The result: Findings suggest that activating SHP1 could be a therapeutic approach for immune-mediated pulmonary diseases, expanding the genetic landscape of inflammatory lung conditions.