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

Biallelic loss-of-function variants in PTPN6 cause 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 diseases is crucial for developing targeted therapies, especially for cases linked to immune system dysfunctions.
• What they did: Researchers identified and characterized seven children with PTPN6 variants that destabilize SHP1 and eliminate its phosphatase activity, revealing a novel inborn error of immunity.
• The result: This discovery broadens the genetic understanding of inflammatory lung conditions and indicates that activating SHP1 could be a promising therapeutic approach for immune-related pulmonary diseases.