A de novo nonsense mutation in the tyrosine kinase lyn in a patient with an early onset autoinflammatory phenotype

Lyn kinase is a Src-family tyrosine kinase expressed by hematopoietic and non-hematopoietic cell types. It functions as an activactor and an inhibitor of signaling pathways. Phosphorylation of a tyrosine residue at position 508 keeps the molecule in an inactive form. Lynup/up mice have a gain-of-function mutation generated at the tyrosine position 508 (Y508F) and present with severe anemia, autoimmune glomerulonephritis and positive ANA. Using whole exome sequencing (WES), we identified a pediatric patient with a nonsense de novo mutation in lyn kinase presenting with an early-onset autoinflammatory phenotype.