| Literature DB >> 25129144 |
Kaan Boztug1, Päivi M Järvinen2, Elisabeth Salzer3, Tomas Racek2, Sebastian Mönch2, Wojciech Garncarz3, E Michael Gertz4, Alejandro A Schäffer4, Aristotelis Antonopoulos5, Stuart M Haslam5, Lena Schieck6, Jacek Puchałka2, Jana Diestelhorst7, Giridharan Appaswamy6, Brigitte Lescoeur8, Roberto Giambruno3, Johannes W Bigenzahn3, Ulrich Elling9, Dietmar Pfeifer10, Cecilia Domínguez Conde3, Michael H Albert2, Karl Welte6, Gudrun Brandes11, Roya Sherkat12, Jutte van der Werff Ten Bosch13, Nima Rezaei14, Amos Etzioni15, Christine Bellanné-Chantelot16, Giulio Superti-Furga3, Josef M Penninger9, Keiryn L Bennett3, Julia von Blume17, Anne Dell5, Jean Donadieu18, Christoph Klein2.
Abstract
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.Entities:
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Year: 2014 PMID： 25129144 PMCID： PMC4829076 DOI： 10.1038/ng.3069
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330