A rare case of syndromic severe congenital neutropenia: JAGN1 mutation

被引：4

作者：

Cipe, Funda Erol ^{[1
]}

Aydogmus, Cigdem ^{[1
]}

Baskin, Kubra ^{[1
]}

Keskindemirci, Gonca ^{[1
,2
]}

Garncarz, Wojciech ^{[3
,4
]}

Boztug, Kaan ^{[3
,4
]}

机构：

[1] Kanuni Sultan Suleyman Training & Res Hosp, Dept Pediat Allergy & Immunol, Istanbul, Turkey

[2] Istanbul Univ Inst Child Hlth, Dept Social Pediat, Istanbul, Turkey

[3] Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria

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

来源：

TURKISH JOURNAL OF PEDIATRICS | 2020年 / 62卷 / 02期

关键词：

severe congenital neutropenia; JAGN1; mutation; GENE;

D O I：

10.24953/turkjped.2020.02.022

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

Background. Neutrophils are essential innate cells to fight bacterial and fungal pathogens. Jagunal homolog 1 (JAGN1) mutations were recently defined as rare genetic defects causing severe congenital neutropenia. JAGN1 participates in the secretory pathway and is required for granulocyte colony-stimulating factor receptor-mediated signalling. This gene is required for normal ultrastructure and granulation of endoplasmic reticulum of myeloid progenitor cells. Its defect is related to increased predisposition to apoptosis. In the literature, a few cases have been reported with congenital anomalies such as cardiac and renal anomalies. Case. Here we report a patient in which JAGN1 deficiency was found after several years. Apart from syndromic facial appearance we were unable to detect any other systemic malformations. Conclusion. The causes of multisystemic features of mutations in JAGN1 gene remain unknown. JAGN1 mutations must be considered in patients with severe congenital neutropenia especially with facial dismorphism even in the absence of systemic manifestations.

引用

页码：326 / 331

页数：6

共 10 条

[1] JAGN1 Deficient Severe Congenital Neutropenia: Two Cases from the Same Family [J].

Baris, S. ;

Karakoc-Aydiner, E. ;

Ozen, A. ;

Delil, K. ;

Kiykim, A. ;

Ogulur, I. ;

Baris, I. ;

Barlan, I. B. .

JOURNAL OF CLINICAL IMMUNOLOGY, 2015, 35 (04) :339-343

[2] JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia [J].

Boztug, Kaan ;

Jaervinen, Paeivi M. ;

Salzer, Elisabeth ;

Racek, Tomas ;

Moench, Sebastian ;

Garncarz, Wojciech ;

Gertz, E. Michael ;

Schaeffer, Alejandro A. ;

Antonopoulos, Aristotelis ;

Haslam, Stuart M. ;

Schieck, Lena ;

Puchalka, Jacek ;

Diestelhorst, Jana ;

Appaswamy, Giridharan ;

Lescoeur, Brigitte ;

Giambruno, Roberto ;

Bigenzahn, Johannes W. ;

Elling, Ulrich ;

Pfeifer, Dietmar ;

Conde, Cecilia Dominguez ;

Albert, Michael H. ;

Welte, Karl ;

Brandes, Gudrun ;

Sherkat, Roya ;

ten Bosch, Jutte van der Werff ;

Rezaei, Nima ;

Etzioni, Amos ;

Bellanne-Chantelot, Christine ;

Superti-Furga, Giulio ;

Penninger, Josef M. ;

Bennett, Keiryn L. ;

von Blume, Julia ;

Dell, Anne ;

Donadieu, Jean ;

Klein, Christoph .

NATURE GENETICS, 2014, 46 (09) :1021-+

[3] A Syndrome with Congenital Neutropenia and Mutations in G6PC3 [J].

Boztug, Kaan ;

Appaswamy, Giridharan ;

Ashikov, Angel ;

Schaffer, Alejandro A. ;

Salzer, Ulrich ;

Diestelhorst, Jana ;

Germeshausen, Manuela ;

Brandes, Gudrun ;

Lee-Gossler, Jacqueline ;

Noyan, Fatih ;

Gatzke, Anna-Katherina ;

Minkov, Milen ;

Greil, Johann ;

Kratz, Christian ;

Petropoulou, Theoni ;

Pellier, Isabelle ;

Bellanne-Chantelot, Christine ;

Rezaei, Nima ;

Moenkemoeller, Kirsten ;

Irani-Hakimeh, Noha ;

Bakker, Hans ;

Gerardy-Schahn, Rita ;

Zeidler, Cornelia ;

Grimbacher, Bodo ;

Welte, Karl ;

Klein, Christoph .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (01) :32-43

[4] Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia [J].

Devriendt, K ;

Kim, AS ;

Mathijs, G ;

Frints, SGM ;

Schwartz, M ;

Van den Oord, JJ ;

Verhoef, GEG ;

Boogaerts, MA ;

Fryns, JP ;

You, DQ ;

Rosen, MK ;

Vandenberghe, P .

NATURE GENETICS, 2001, 27 (03) :313-317

[5] Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis [J].

Grenda, David S. ;

Murakami, Mark ;

Ghatak, Jhuma ;

Xia, Jun ;

Boxer, Laurence A. ;

Dale, David ;

Dinauer, Mary C. ;

Link, Daniel C. .

BLOOD, 2007, 110 (13) :4179-4187

[6] HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease) [J].

Klein, Christoph ;

Grudzien, Magda ;

Appaswamy, Giridharan ;

Germeshausen, Manuela ;

Sandrock, Inga ;

Schaffer, Alejandro A. ;

Rathinam, Chozhavendan ;

Boztug, Kaan ;

Schwinzer, Beate ;

Rezaei, Nima ;

Bohn, Georg ;

Melin, Malin ;

Carlsson, Goran ;

Fadeel, Bengt ;

Dahl, Niklas ;

Palmblad, Jan ;

Henter, Jan-Inge ;

Zeidler, Cornelia ;

Grimbacher, Bodo ;

Welte, Karl .

NATURE GENETICS, 2007, 39 (01) :86-92

[7] Genetic Defects in Severe Congenital Neutropenia: Emerging Insights into Life and Death of Human Neutrophil Granulocytes [J].

Klein, Christoph .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 29, 2011, 29 :399-413

[8] Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2 [J].

Person, RE ;

Li, FQ ;

Duan, ZJ ;

Benson, KF ;

Wechsler, J ;

Papadaki, HA ;

Eliopoulos, G ;

Kaufman, C ;

Bertolone, SJ ;

Nakamoto, B ;

Papayannopoulou, T ;

Grimes, HL ;

Horwitz, M .

NATURE GENETICS, 2003, 34 (03) :308-312

[9] The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy [J].

Stepensky, Polina ;

Saada, Ann ;

Cowan, Marianne ;

Tabib, Adi ;

Fischer, Ute ;

Berkun, Yackov ;

Saleh, Hani ;

Simanovsky, Natalia ;

Kogot-Levin, Aviram ;

Weintraub, Michael ;

Ganaiem, Hamam ;

Shaag, Avraham ;

Zenvirt, Shamir ;

Borkhardt, Arndt ;

Elpeleg, Orly ;

Bryant, Nia J. ;

Mevorach, Dror .

BLOOD, 2013, 121 (25) :5078-5087

[10] Jagunal homolog 1 is a critical regulator of neutrophil function in fungal host defense [J].

Wirnsberger, Gerald ;

Zwolanek, Florian ;

Stadlmann, Johannes ;

Tortola, Luigi ;

Liu, Shang Wan ;

Perlot, Thomas ;

Jaervinen, Paeivi ;

Duenberger, Gerhard ;

Kozieradzki, Ivona ;

Sarao, Renu ;

De Martino, Alba ;

Boztug, Kaan ;

Mechtler, Karl ;

Kuchler, Karl ;

Klein, Christoph ;

Elling, Ulrich ;

Penninger, Josef M. .

NATURE GENETICS, 2014, 46 (09) :1028-+

← 1 →