A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function.


Journal

The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R

Informations de publication

Date de publication:
02 12 2019
Historique:
received: 23 01 2019
revised: 19 04 2019
accepted: 06 08 2019
pubmed: 12 10 2019
medline: 17 6 2020
entrez: 12 10 2019
Statut: ppublish

Résumé

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo

Identifiants

pubmed: 31601675
pii: jem.20190147
doi: 10.1084/jem.20190147
pmc: PMC6888978
doi:

Substances chimiques

CDC42 protein, human EC 3.6.5.2
cdc42 GTP-Binding Protein EC 3.6.5.2

Banques de données

PDB
['1DOA']

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2778-2799

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI067946
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120989
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006542
Pays : United States

Informations de copyright

© 2019 Lam et al.

Références

Hum Mutat. 2013 Sep;34(9):E2393-402
pubmed: 23843252
Pathog Dis. 2018 Apr 1;76(3):
pubmed: 29718184
Nat Genet. 2014 Oct;46(10):1140-6
pubmed: 25217959
J Cell Sci. 2004 Mar 15;117(Pt 8):1291-300
pubmed: 15020669
Blood. 2019 May 2;133(18):1977-1988
pubmed: 30723080
Am J Hum Genet. 2018 Oct 4;103(4):621-630
pubmed: 30290154
Cytometry A. 2017 Oct;91(10):952-965
pubmed: 28609016
Nature. 2002 Dec 12;420(6916):629-35
pubmed: 12478284
J Exp Med. 2015 Jun 1;212(6):927-38
pubmed: 26008898
Blood. 2018 Jul 5;132(1):89-100
pubmed: 29632024
Nature. 1995 Nov 2;378(6552):88-91
pubmed: 7477296
Ann Rheum Dis. 2017 Jan;76(1):166-172
pubmed: 27296321
Am J Hum Genet. 2018 Feb 1;102(2):309-320
pubmed: 29394990
Pediatr Blood Cancer. 2007 Feb;48(2):124-31
pubmed: 16937360
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11351-6
pubmed: 12177428
Sci Rep. 2017 Sep 20;7(1):11978
pubmed: 28931895
J Allergy Clin Immunol. 2017 Jan;139(1):232-245
pubmed: 27577878
Nat Rev Rheumatol. 2016 May;12(5):259-68
pubmed: 27009539
Am J Clin Pathol. 2013 Jun;139(6):713-27
pubmed: 23690113
Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11912-7
pubmed: 20547841
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5091-6
pubmed: 17360364
Am J Hum Genet. 2016 Oct 6;99(4):962-973
pubmed: 27666370
J Biol Chem. 2008 May 16;283(20):14153-64
pubmed: 18348980
Biochemistry. 2013 Jun 25;52(25):4354-63
pubmed: 23718289
Methods Mol Biol. 2010;612:335-52
pubmed: 20033652
Blood. 2018 Nov 29;132(22):2362-2374
pubmed: 30254128
Blood. 2011 Oct 13;118(15):4041-52
pubmed: 21828139
Exp Cell Res. 2004 Dec 10;301(2):211-22
pubmed: 15530857
Cell. 2000 Feb 4;100(3):345-56
pubmed: 10676816
Biochem J. 2001 Oct 15;359(Pt 2):285-94
pubmed: 11583574
Scand J Immunol. 2012 Apr;75(4):455-62
pubmed: 22150284
Science. 2003 Dec 5;302(5651):1704-9
pubmed: 14657486
Blood. 2017 Aug 3;130(5):677-685
pubmed: 28588018
Nat Genet. 2014 Oct;46(10):1135-1139
pubmed: 25217960
Nat Commun. 2014 Sep 11;5:4839
pubmed: 25208761
Fly (Austin). 2012 Apr-Jun;6(2):80-92
pubmed: 22728672
Biochim Biophys Acta. 2011 Dec;1808(12):2981-94
pubmed: 21819967
MBio. 2014 Jul 01;5(4):e01402-14
pubmed: 24987096
J Biol Chem. 2002 Jul 5;277(27):24753-63
pubmed: 11948177
Nat Genet. 2014 Mar;46(3):310-5
pubmed: 24487276
Small GTPases. 2017 Jun 16;:1-7
pubmed: 28622072
Curr Opin Immunol. 2017 Dec;49:20-26
pubmed: 28866302
Cell. 2002 Jun 28;109(7):873-85
pubmed: 12110184
PLoS Biol. 2018 Jul 9;16(7):e2005380
pubmed: 29985916
Am J Med Genet A. 2015 Nov;167A(11):2822-5
pubmed: 26386261
Blood. 2007 Dec 1;110(12):3853-61
pubmed: 17702896
Curr Opin Cell Biol. 2015 Oct;36:23-31
pubmed: 26186729
Curr Rheumatol Rep. 2018 May 30;20(7):40
pubmed: 29846819
Clin Immunol. 2011 Nov;141(2):128-32
pubmed: 21763205
EMBO Rep. 2004 Dec;5(12):1130-6
pubmed: 15577926
Nat Rev Mol Cell Biol. 2008 Jun;9(6):446-54
pubmed: 18464790
Nat Genet. 2015 Nov;47(11):1334-40
pubmed: 26457648
Blood. 2018 Mar 29;131(13):1442-1455
pubmed: 29326099
Nat Genet. 2016 Dec;48(12):1581-1586
pubmed: 27776117
WormBook. 2018 Aug 16;2018:1-65
pubmed: 27218782

Auteurs

Michael T Lam (MT)

Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Department of Pediatrics, Columbia University, Irving Medical Center, New York, NY.
Medical Scientist Training Program and Translational Biology and Molecular Medicine Graduate Program, Baylor College of Medicine, Houston, TX.

Simona Coppola (S)

National Center for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy.

Oliver H F Krumbach (OHF)

Institute of Biochemistry and Molecular Biology II, Medical Faculty of the Heinrich-Heine University, Düsseldorf, Germany.

Giusi Prencipe (G)

Immunology Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Antonella Insalaco (A)

Immunology Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Cristina Cifaldi (C)

Academic Department of Pediatrics, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Immacolata Brigida (I)

San Raffaele Telethon Institute for Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.

Erika Zara (E)

National Center for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy.

Serena Scala (S)

San Raffaele Telethon Institute for Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.

Silvia Di Cesare (S)

Academic Department of Pediatrics, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Simone Martinelli (S)

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.

Martina Di Rocco (M)

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Department of Cellular Biotechnology and Haematology, Sapienza University of Rome, Rome, Italy.

Antonia Pascarella (A)

Immunology Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Marcello Niceta (M)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Francesca Pantaleoni (F)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Andrea Ciolfi (A)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Petra Netter (P)

Department of Pediatrics, Baylor College of Medicine, Houston, TX.

Alexandre F Carisey (AF)

Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Department of Pediatrics, Columbia University, Irving Medical Center, New York, NY.

Michael Diehl (M)

Department of Bioengineering, Rice University, Houston, TX.

Mohammad Akbarzadeh (M)

Institute of Biochemistry and Molecular Biology II, Medical Faculty of the Heinrich-Heine University, Düsseldorf, Germany.

Francesca Conti (F)

Academic Department of Pediatrics, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Pietro Merli (P)

Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Anna Pastore (A)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Stefano Levi Mortera (S)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Serena Camerini (S)

Core Facilities, Italian National Institute of Health, Rome, Italy.

Luciapia Farina (L)

National Center for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy.
Immunology Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Marcel Buchholzer (M)

Institute of Biochemistry and Molecular Biology II, Medical Faculty of the Heinrich-Heine University, Düsseldorf, Germany.

Luca Pannone (L)

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Tram N Cao (TN)

Department of Pediatrics, Baylor College of Medicine, Houston, TX.

Zeynep H Coban-Akdemir (ZH)

Baylor-Hopkins Center for Mendelian Genomics, Houston, TX.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.

Shalini N Jhangiani (SN)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
Human Genome Sequencing Center of Baylor College of Medicine, Houston, TX.

Donna M Muzny (DM)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
Human Genome Sequencing Center of Baylor College of Medicine, Houston, TX.

Richard A Gibbs (RA)

Baylor-Hopkins Center for Mendelian Genomics, Houston, TX.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
Human Genome Sequencing Center of Baylor College of Medicine, Houston, TX.

Luca Basso-Ricci (L)

San Raffaele Telethon Institute for Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.

Maria Chiriaco (M)

Academic Department of Pediatrics, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Radovan Dvorsky (R)

Institute of Biochemistry and Molecular Biology II, Medical Faculty of the Heinrich-Heine University, Düsseldorf, Germany.

Lorenza Putignani (L)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Rita Carsetti (R)

Immunology Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Petra Janning (P)

Department of Chemical Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.

Asbjorg Stray-Pedersen (A)

Baylor-Hopkins Center for Mendelian Genomics, Houston, TX.
Norwegian National Unit for Newborn Screening, Department of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Hans Christian Erichsen (HC)

Department of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.

AnnaCarin Horne (A)

Pediatric Rheumatology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.

Yenan T Bryceson (YT)

Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Broegelmann Research Laboratory, Institute of Clinical Sciences, University of Bergen, Bergen, Norway.

Lamberto Torralba-Raga (L)

Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.

Kim Ramme (K)

Pediatric Hematology, Immunology and HCT Section, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.

Vittorio Rosti (V)

Center for Myelofibrosis, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.

Claudia Bracaglia (C)

Immunology Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Virginia Messia (V)

Immunology Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Paolo Palma (P)

Academic Department of Pediatrics, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

Andrea Finocchi (A)

Academic Department of Pediatrics, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Franco Locatelli (F)

Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Department of Pediatrics, Sapienza University of Rome, Italy.

Ivan K Chinn (IK)

Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Division of Pediatric Immunology, Allergy, Rheumatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.

James R Lupski (JR)

Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Baylor-Hopkins Center for Mendelian Genomics, Houston, TX.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
Human Genome Sequencing Center of Baylor College of Medicine, Houston, TX.

Emily M Mace (EM)

Department of Pediatrics, Columbia University, Irving Medical Center, New York, NY.

Caterina Cancrini (C)

Academic Department of Pediatrics, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Alessandro Aiuti (A)

San Raffaele Telethon Institute for Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.
Pediatric Immunohematology, San Raffaele Scientific Institute, Milan, Italy.
Vita Salute San Raffaele University, Milan, Italy.

Mohammad R Ahmadian (MR)

Institute of Biochemistry and Molecular Biology II, Medical Faculty of the Heinrich-Heine University, Düsseldorf, Germany reza.ahmadian@hhu.de.

Jordan S Orange (JS)

Department of Pediatrics, Columbia University, Irving Medical Center, New York, NY jso2121@cumc.columbia.edu.
Medical Scientist Training Program and Translational Biology and Molecular Medicine Graduate Program, Baylor College of Medicine, Houston, TX.

Fabrizio De Benedetti (F)

Immunology Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy fabrizio.debenedetti@opbg.net.

Marco Tartaglia (M)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy marco.tartaglia@opbg.net.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH