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Next-Generation Sequencing Reveals A JAGN1 Mutation in a Syndromic Child With Intermittent Neutropenia

Cifaldi, Cristina, PhD*; Serafinelli, Jessica, MD*; Petricone, Davide, BS; Brigida, Immacolata, PhD; Di Cesare, Silvia, PhD*; Di Matteo, Gigliola, PhD; Chiriaco, Maria, PhD*; De Vito, Rita, MD§; Palumbo, Giuseppe, MD; Rossi, Paolo, MD*,†; Palma, Paolo, MD*; Cancrini, Caterina, MD, PhD*,†; Aiuti, Alessandro, MD, PhD‡,¶,#; Finocchi, Andrea, MD, PhD*,†

Journal of Pediatric Hematology/Oncology: May 2019 - Volume 41 - Issue 4 - p e266–e269
doi: 10.1097/MPH.0000000000001256
Online Articles: Clinical and Laboratory Observations

Background: Jagunal homolog 1 (JAGN1) gene was identified as a novel responsible for severe congenital neutropenia. The protein encoded by this gene is required for neutrophil differentiation, survival and function in microbial activity. JAGN1-deficient human neutrophils are characterized by alterations in trafficking within the endoplasmic reticulum and golgi compartments because of ultrastructural defects in endoplasmic reticulum and susceptibility to apoptosis.

Observations: We report a patient exhibiting an intermittent neutropenia, for which a next-generation sequencing revealed a homozygous mutation in the JAGN1 gene.

Conclusions: The patient extends the clinical variability associated to JAGN1 mutations, and this case highlights the importance of genetic investigations in patients with suspected neutropenia.

*University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens’ Hospital Bambino Gesù

§Department of Pathology and Molecular Histopathology, Bambino Gesù Children’s Hospital IRCCS

University Department of Pediatrics, Unit of Hematology and Oncology, Bambino Gesù Children’s Hospital

Department of Systems Medicine, “University of Rome Tor Vergata,” Rome

San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute

Vita Salute San Raffaele University

#Pediatric Immunohematology, San Raffaele Scientific Institute, Milan, Italy

C.C. and J.S. contributed equally.

Supported by the European Commission—Advanced Cell-based Therapies for the Treatment of Primary Immunodeficiency (HEALTH-F5-2010-261387, CELL-PID), Fondazione Roma and Italian Ministero della Salute (NET-2011-02350069), and Ospedale Pediatrico Bambino Gesù Ricerca Corrente (201602P003708), the European Commission (ERARE-3-JTC 2015 EUROCID), and Fondazione Telethon (TIGET Core grant C6).

The authors declare no conflict of interest.

Reprints: Andrea Finocchi, MD, PhD, University of Rome Tor Vergata and DPUO-Childrens’ Hospital Bambino Gesù, Via Montpellier, 1, Roma RM 00133, Italy (e-mail:

Received November 13, 2017

Accepted June 10, 2018

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