Boztug Kaan, Järvinen Päivi M, Salzer Elisabeth, Racek Tomas, Mönch Sebastian, Garncarz Wojciech, Gertz E Michael, Schäffer Alejandro A, Antonopoulos Aristotelis, Haslam Stuart M, Schieck Lena, Puchałka Jacek, Diestelhorst Jana, Appaswamy Giridharan, Lescoeur Brigitte, Giambruno Roberto, Bigenzahn Johannes W, Elling Ulrich, Pfeifer Dietmar, Conde Cecilia Domínguez, Albert Michael H, Welte Karl, Brandes Gudrun, Sherkat Roya, van der Werff Ten Bosch Jutte, Rezaei Nima, Etzioni Amos, Bellanné-Chantelot Christine, Superti-Furga Giulio, Penninger Josef M, Bennett Keiryn L, von Blume Julia, Dell Anne, Donadieu Jean, Klein Christoph
1] CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. [2] Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany.
Nat Genet. 2014 Sep;46(9):1021-7. doi: 10.1038/ng.3069. Epub 2014 Aug 17.
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.
对严重先天性中性粒细胞减少症（SCN）患者的分析，可能有助于揭示控制中性粒细胞分化、维持和衰退的各种因素之间的微妙平衡。我们在14例SCN患者中，鉴定出编码Jagunal同源物1的JAGN1基因存在9种不同的纯合突变。JAGN1突变的粒细胞具有超微结构缺陷、颗粒稀少、多种蛋白质N-糖基化异常以及凋亡发生率增加等特征。JAGN1参与分泌途径，是粒细胞集落刺激因子受体介导信号传导所必需的。JAGN1是中性粒细胞分化和存活所必需的一个因子。
