JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.
JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.
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DOI：
10.1038/ng.3069
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发表时间：
2014-09
期刊：
影响因子：
30.8
通讯作者：
Klein C
中科院分区：
文献类型：
--
作者：
Boztug K;Järvinen PM;Salzer E;Racek T;Mönch S;Garncarz W;Gertz EM;Schäffer AA;Antonopoulos A;Haslam SM;Schieck L;Puchałka J;Diestelhorst J;Appaswamy G;Lescoeur B;Giambruno R;Bigenzahn JW;Elling U;Pfeifer D;Conde CD;Albert MH;Welte K;Brandes G;Sherkat R;van der Werff Ten Bosch J;Rezaei N;Etzioni A;Bellanné-Chantelot C;Superti-Furga G;Penninger JM;Bennett KL;von Blume J;Dell A;Donadieu J;Klein C
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、维持和衰退的因素之间的微妙平衡。我们在14例SCN患者中发现了编码Jagunal Homolog 1(JAGN1)基因的9个不同的纯合子突变。JAGN1突变的粒细胞以超微结构缺陷、颗粒稀少、多种蛋白质的N-糖基化异常和细胞凋亡增加为特征。JAGN1参与分泌途径，是粒细胞集落刺激因子受体介导的信号转导所必需的。JAGN1是中性粒细胞分化和存活所必需的一个因子。
Analysis of patients with severe congenital neutropenia (SCN) may shed light on the delicate balance of factors controlling differentiation, maintenance, and decay of neutrophils. We identify 9 distinct homozygous mutations in the gene encoding Jagunal homolog 1 (JAGN1) in 14 SCN patients. JAGN1-mutant granulocytes are characterized by ultrastructural defects, paucity of granules, aberrant N-glycosylation of multiple proteins, and increased apoptosis. JAGN1 participates in the secretory pathway and is required for granulocyte-colony stimulating factor receptor-mediated signaling. JAGN1 emerges as a factor necessary in differentiation and survival of neutrophils.