Nature Genetics 2014-09-01

JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.

Kaan Boztug, Päivi M Järvinen, Elisabeth Salzer, Tomas Racek, Sebastian Mönch, Wojciech Garncarz, E Michael Gertz, Alejandro A Schäffer, Aristotelis Antonopoulos, Stuart M Haslam, Lena Schieck, Jacek Puchałka, Jana Diestelhorst, Giridharan Appaswamy, Brigitte Lescoeur, Roberto Giambruno, Johannes W Bigenzahn, Ulrich Elling, Dietmar Pfeifer, Cecilia Domínguez Conde, Michael H Albert, Karl Welte, Gudrun Brandes, Roya Sherkat, Jutte van der Werff Ten Bosch, Nima Rezaei, Amos Etzioni, Christine Bellanné-Chantelot, Giulio Superti-Furga, Josef M Penninger, Keiryn L Bennett, Julia von Blume, Anne Dell, Jean Donadieu, Christoph Klein

文献索引：Nat. Genet. 46(9) , 1021-7, (2014)

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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.