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Merck
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  • JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.

JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.

Nature genetics (2014-08-19)
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
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.

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