JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.
Kaan BoztugPäivi M JärvinenElisabeth SalzerTomas RacekSebastian MönchWojciech GarncarzE Michael GertzAlejandro A SchäfferAristotelis AntonopoulosStuart M HaslamLena SchieckJacek PuchałkaJana DiestelhorstGiridharan AppaswamyBrigitte LescoeurRoberto GiambrunoJohannes W BigenzahnUlrich EllingDietmar PfeiferCecilia Domínguez CondeMichael H AlbertKarl WelteGudrun BrandesRoya SherkatJutte van der Werff Ten BoschNima RezaeiAmos EtzioniChristine Bellanné-ChantelotGiulio Superti-FurgaJosef M PenningerKeiryn L BennettJulia von BlumeAnne DellJean DonadieuChristoph KleinPublished in: Nature genetics (2014)
The analysis of individuals with severe congenital neutropenia (SCN) may shed light on the delicate balance of factors controlling the differentiation, maintenance and decay of neutrophils. We identify 9 distinct homozygous mutations in the JAGN1 gene encoding Jagunal homolog 1 in 14 individuals with SCN. JAGN1-mutant granulocytes are characterized by ultrastructural defects, a paucity of granules, aberrant N-glycosylation of multiple proteins and increased incidence of apoptosis. JAGN1 participates in the secretory pathway and is required for granulocyte colony-stimulating factor receptor-mediated signaling. JAGN1 emerges as a factor that is necessary in the differentiation and survival of neutrophils.