JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia

被引：102

作者：

Boztug, Kaan ^{[1
,2
]}

Jaervinen, Paeivi M. ^{[3
]}

Salzer, Elisabeth ^{[1
]}

Racek, Tomas ^{[3
]}

Moench, Sebastian ^{[3
]}

Garncarz, Wojciech ^{[1
]}

Gertz, E. Michael ^{[4
]}

Schaeffer, Alejandro A. ^{[4
]}

Antonopoulos, Aristotelis ^{[5
]}

Haslam, Stuart M. ^{[5
]}

Schieck, Lena ^{[6
]}

Puchalka, Jacek ^{[3
]}

Diestelhorst, Jana ^{[3
,6
]}

Appaswamy, Giridharan ^{[6
]}

Lescoeur, Brigitte ^{[7
]}

Giambruno, Roberto ^{[1
]}

Bigenzahn, Johannes W. ^{[1
]}

Elling, Ulrich ^{[8
]}

Pfeifer, Dietmar ^{[9
]}

Conde, Cecilia Dominguez ^{[1
,12
]}

Albert, Michael H. ^{[3
]}

Welte, Karl ^{[6
]}

Brandes, Gudrun ^{[10
]}

Sherkat, Roya ^{[11
]}

ten Bosch, Jutte van der Werff

Rezaei, Nima ^{[13
]}

Etzioni, Amos ^{[14
]}

Bellanne-Chantelot, Christine ^{[15
]}

Superti-Furga, Giulio ^{[1
]}

Penninger, Josef M.

Bennett, Keiryn L. ^{[1
]}

von Blume, Julia ^{[16
]}

Dell, Anne ^{[5
]}

Donadieu, Jean ^{[17
]}

Klein, Christoph ^{[3
]}

机构：

[1] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1010 Vienna, Austria

[2] Med Univ Vienna, Dept Pediat & Adolescent Med, Vienna, Austria

[3] Univ Munich, Dr von Hauner Childrens Hosp, Dept Pediat, Munich, Germany

[4] US Natl Inst Hlth, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD USA

[5] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London, England

[6] Hannover Med Sch, Dept Pediat Hematol Oncol, Hannover, Germany

[7] Hosp R Debre, Dept Hematol, Paris, France

[8] Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna, Austria

[9] Univ Med Ctr Freiburg, Dept Hematol Oncol & Stem Cell Transplantat, Freiburg, Germany

[10] Hannover Med Sch, Dept Cell Biol, Hannover, Germany

[11] Isfahan Univ Med Sci, Acquired Immunodeficiency Res Ctr, Esfahan, Iran

[12] Hosp Free Univ Brussels, Dept Pediat, Brussels, Belgium

[13] Univ Tehran Med Sci, Childrens Med Ctr, Pediat Ctr Excellence, Res Ctr Immunodeficiencies, Tehran, Iran

[14] Technion Israel Inst Technol, Rappaport Sch Med, Div Pediat & Immunol, Haifa, Israel

[15] Univ Paris 06, Hop La Pitie Salpetriere, AP HP, Dept Genet, Paris, France

[16] Max Planck Inst Biochem, D-82152 Martinsried, Germany

[17] Armand Trousseau Childrens Hosp, AP HP, Reference Ctr Hereditary Immunodeficiencies, Neutropenia Registry, Paris, France

来源：

NATURE GENETICS | 2014年 / 46卷 / 09期

基金：

欧洲研究理事会; 英国生物技术与生命科学研究理事会; 美国国家卫生研究院; 奥地利科学基金会;

关键词：

STIMULATING FACTOR-RECEPTOR; UNFOLDED PROTEIN RESPONSE; HERMANSKY-PUDLAK-SYNDROME; ENDOPLASMIC-RETICULUM; MASS-SPECTROMETRY; ELANE MUTATIONS; SEQUENCING DATA; COHEN-SYNDROME; GENE; ELASTASE;

D O I：

10.1038/ng.3069

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1021 / +

页数：10

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