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

PTPN6

Biallelic loss-of-function PTPN6 variants destabilizing the immunoregulatory phosphatase SHP1 and abolishing its phosphatase activity

Severe inflammatory lung disease, including acute respiratory distress syndrome (ARDS), has diverse causes, a subset of which are inborn errors of immunity. The authors describe a novel inborn error of immunity caused by biallelic loss-of-function variants in PTPN6, which encodes the immunoregulatory phosphatase SHP1. Seven children from five families developed early-onset anemia and severe inflammatory lung disease, at times presenting as ARDS. The causative variants destabilize SHP1 and abolish its phosphatase activity, and the authors suggest SHP1 activation as a potential therapeutic strategy.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

PTPN6 is not a new gene: it was already associated with familial emphysema in the heterozygous state, and this work describes a distinct recessive form, which requires keeping the two contexts apart at interpretation. The gene should be examined on exome or genome data in a child with severe inflammatory lung disease and anemia. The therapeutic avenue of SHP1 activation remains a hypothesis at this stage.

Analysis by Dr Thibaut Benquey