Congenital immunodeficiencies comprise a group of disorders characterized by an abnormal immune system. The body’s ability to fight infections is impaired and infections can have life-threatening consequences for those affected. Analysis of patients with a disease characterized by an inherited lack of neutrophil granulocytes termed severe congenital neutropenia (SCN) may shed light on the delicate balance of factors controlling differentiation, maintenance, and decay of neutrophils. The team of CeMM Principal Investigator Kaan Boztug in collaboration with the group of Christoph Klein, Director of the Dr. Von Hauner Children’s Hospital Munich, identified mutations in the gene JAGN1 as a novel subtype of SCN in 14 patients bearing 9 distinct JAGN1 mutations. JAGN1 deficiency accounts for approximately 10% SCN for which the underlying genetic defect had previously been unknown. The researchers could show that JAGN1 mutations lead to aberrant function of the endoplasmic reticulum, defective protein glycosylation and increased neutrophil apoptosis. SCN patients are usually treated with the cytokine G-CSF, however for JAGN1-deficient patients the treatment response was unsatisfactory. In a second study IMBA Director Josef Penninger and his team generated Jagn1 knock-out mice and could show that GM-CSF, but not G-CSF, treatment rescues the defects of JAGN1-deficient neutrophils in mice.