HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease.
Identifieur interne : 000114 ( Main/Exploration ); précédent : 000113; suivant : 000115HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease.
Auteurs : Sarah A. Cook [États-Unis] ; William A. Comrie [États-Unis] ; M Cecilia Poli [États-Unis, Chili] ; Morgan Similuk [États-Unis] ; Andrew J. Oler [États-Unis] ; Aiman J. Faruqi [États-Unis] ; Douglas B. Kuhns [États-Unis] ; Sheng Yang [États-Unis] ; Alexander Vargas-Hernández [États-Unis] ; Alexandre F. Carisey [États-Unis] ; Benjamin Fournier [France] ; D Eric Anderson [États-Unis] ; Susan Price [États-Unis] ; Margery Smelkinson [États-Unis] ; Wadih Abou Chahla [France] ; Lisa R. Forbes [États-Unis] ; Emily M. Mace [États-Unis] ; Tram N. Cao [États-Unis] ; Zeynep H. Coban-Akdemir [États-Unis] ; Shalini N. Jhangiani [États-Unis] ; Donna M. Muzny [États-Unis] ; Richard A. Gibbs [États-Unis] ; James R. Lupski [États-Unis] ; Jordan S. Orange [États-Unis] ; Geoffrey D E. Cuvelier [Canada] ; Moza Al Hassani [Émirats arabes unis] ; Nawal Al Kaabi [Émirats arabes unis] ; Zain Al Yafei [Émirats arabes unis] ; Soma Jyonouchi [États-Unis] ; Nikita Raje [États-Unis] ; Jason W. Caldwell [États-Unis] ; Yanping Huang [États-Unis] ; Janis K. Burkhardt [États-Unis] ; Sylvain Latour [France] ; Baoyu Chen [États-Unis] ; Gehad Elghazali [Émirats arabes unis] ; V Koneti Rao [États-Unis] ; Ivan K. Chinn [États-Unis] ; Michael J. Lenardo [États-Unis]Source :
- Science (New York, N.Y.) [ 1095-9203 ] ; 2020.
Descripteurs français
- KwdFr :
- Actines (métabolisme), Complexe-2 cible mécanistique de la rapamycine (métabolisme), Cytokines (biosynthèse), Déficits immunitaires (génétique), Déficits immunitaires (immunologie), Facteur-1 d'ADP-ribosylation (métabolisme), Famille de protéines du syndrome de Wiskott-Aldrich (composition chimique), Famille de protéines du syndrome de Wiskott-Aldrich (métabolisme), Humains (MeSH), Lymphocytes T CD4+ (immunologie), Pedigree (MeSH), Phosphorylation (MeSH), Prolifération cellulaire (MeSH), Protéines membranaires (génétique), Protéines membranaires (physiologie), Syndromes lymphoprolifératifs (génétique), Syndromes lymphoprolifératifs (immunologie).
- MESH :
- biosynthèse : Cytokines.
- composition chimique : Famille de protéines du syndrome de Wiskott-Aldrich.
- génétique : Déficits immunitaires, Protéines membranaires, Syndromes lymphoprolifératifs.
- immunologie : Déficits immunitaires, Lymphocytes T CD4+, Syndromes lymphoprolifératifs.
- métabolisme : Actines, Complexe-2 cible mécanistique de la rapamycine, Facteur-1 d'ADP-ribosylation, Famille de protéines du syndrome de Wiskott-Aldrich.
- physiologie : Protéines membranaires.
- Humains, Pedigree, Phosphorylation, Prolifération cellulaire.
English descriptors
- KwdEn :
- ADP-Ribosylation Factor 1 (metabolism), Actins (metabolism), CD4-Positive T-Lymphocytes (immunology), Cell Proliferation (MeSH), Cytokines (biosynthesis), Humans (MeSH), Immunologic Deficiency Syndromes (genetics), Immunologic Deficiency Syndromes (immunology), Lymphoproliferative Disorders (genetics), Lymphoproliferative Disorders (immunology), Mechanistic Target of Rapamycin Complex 2 (metabolism), Membrane Proteins (genetics), Membrane Proteins (physiology), Pedigree (MeSH), Phosphorylation (MeSH), Wiskott-Aldrich Syndrome Protein Family (chemistry), Wiskott-Aldrich Syndrome Protein Family (metabolism).
- MESH :
- chemical , biosynthesis : Cytokines.
- chemical , chemistry : Wiskott-Aldrich Syndrome Protein Family.
- chemical , genetics : Membrane Proteins.
- chemical , metabolism : ADP-Ribosylation Factor 1, Actins, Mechanistic Target of Rapamycin Complex 2, Wiskott-Aldrich Syndrome Protein Family.
- genetics : Immunologic Deficiency Syndromes, Lymphoproliferative Disorders.
- immunology : CD4-Positive T-Lymphocytes, Immunologic Deficiency Syndromes, Lymphoproliferative Disorders.
- chemical , physiology : Membrane Proteins.
- Cell Proliferation, Humans, Pedigree, Phosphorylation.
Abstract
Immunodeficiency often coincides with hyperactive immune disorders such as autoimmunity, lymphoproliferation, or atopy, but this coincidence is rarely understood on a molecular level. We describe five patients from four families with immunodeficiency coupled with atopy, lymphoproliferation, and cytokine overproduction harboring mutations in NCKAP1L, which encodes the hematopoietic-specific HEM1 protein. These mutations cause the loss of the HEM1 protein and the WAVE regulatory complex (WRC) or disrupt binding to the WRC regulator, Arf1, thereby impairing actin polymerization, synapse formation, and immune cell migration. Diminished cortical actin networks caused by WRC loss led to uncontrolled cytokine release and immune hyperresponsiveness. HEM1 loss also blocked mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, T cell proliferation, and selected effector functions, leading to immunodeficiency. Thus, the evolutionarily conserved HEM1 protein simultaneously regulates filamentous actin (F-actin) and mTORC2 signaling to achieve equipoise in immune responses.
DOI: 10.1126/science.aay5663
PubMed: 32647003
Affiliations:
- Canada, Chili, France, Émirats arabes unis, États-Unis
- Caroline du Nord, Hauts-de-France, Iowa, Manitoba, Maryland, Missouri (État), Nord-Pas-de-Calais, Pennsylvanie, Texas, État de New York, Île-de-France
- Ames (Iowa), Lille, Paris, Winnipeg
- Université d'État de l'Iowa, Université du Manitoba
Links toward previous steps (curation, corpus...)
Le document en format XML
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Forbes</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Mace, Emily M" sort="Mace, Emily M" uniqKey="Mace E" first="Emily M" last="Mace">Emily M. Mace</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Columbia University Irving Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Cao, Tram N" sort="Cao, Tram N" uniqKey="Cao T" first="Tram N" last="Cao">Tram N. Cao</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Coban Akdemir, Zeynep H" sort="Coban Akdemir, Zeynep H" uniqKey="Coban Akdemir Z" first="Zeynep H" last="Coban-Akdemir">Zeynep H. Coban-Akdemir</name><affiliation wicri:level="2"><nlm:affiliation>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Jhangiani, Shalini N" sort="Jhangiani, Shalini N" uniqKey="Jhangiani S" first="Shalini N" last="Jhangiani">Shalini N. Jhangiani</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Muzny, Donna M" sort="Muzny, Donna M" uniqKey="Muzny D" first="Donna M" last="Muzny">Donna M. Muzny</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Gibbs, Richard A" sort="Gibbs, Richard A" uniqKey="Gibbs R" first="Richard A" last="Gibbs">Richard A. Gibbs</name><affiliation wicri:level="2"><nlm:affiliation>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Lupski, James R" sort="Lupski, James R" uniqKey="Lupski J" first="James R" last="Lupski">James R. Lupski</name><affiliation wicri:level="2"><nlm:affiliation>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Orange, Jordan S" sort="Orange, Jordan S" uniqKey="Orange J" first="Jordan S" last="Orange">Jordan S. Orange</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Columbia University Irving Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Cuvelier, Geoffrey D E" sort="Cuvelier, Geoffrey D E" uniqKey="Cuvelier G" first="Geoffrey D E" last="Cuvelier">Geoffrey D E. Cuvelier</name><affiliation wicri:level="4"><nlm:affiliation>Section of Pediatric Hematology/Oncology/BMT, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Section of Pediatric Hematology/Oncology/BMT, CancerCare Manitoba, University of Manitoba, Winnipeg, MB</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Al Hassani, Moza" sort="Al Hassani, Moza" uniqKey="Al Hassani M" first="Moza" last="Al Hassani">Moza Al Hassani</name><affiliation wicri:level="1"><nlm:affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author><author><name sortKey="Al Kaabi, Nawal" sort="Al Kaabi, Nawal" uniqKey="Al Kaabi N" first="Nawal" last="Al Kaabi">Nawal Al Kaabi</name><affiliation wicri:level="1"><nlm:affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author><author><name sortKey="Al Yafei, Zain" sort="Al Yafei, Zain" uniqKey="Al Yafei Z" first="Zain" last="Al Yafei">Zain Al Yafei</name><affiliation wicri:level="1"><nlm:affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author><author><name sortKey="Jyonouchi, Soma" sort="Jyonouchi, Soma" uniqKey="Jyonouchi S" first="Soma" last="Jyonouchi">Soma Jyonouchi</name><affiliation wicri:level="2"><nlm:affiliation>Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Raje, Nikita" sort="Raje, Nikita" uniqKey="Raje N" first="Nikita" last="Raje">Nikita Raje</name><affiliation wicri:level="2"><nlm:affiliation>Division of Allergy, Immunology, Pulmonary, and Sleep Medicine, Children's Mercy Hospital, Kansas City, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Allergy, Immunology, Pulmonary, and Sleep Medicine, Children's Mercy Hospital, Kansas City, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Internal Medicine and Pediatrics, University of Missouri Kansas City, Kansas City, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine and Pediatrics, University of Missouri Kansas City, Kansas City, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region></placeName></affiliation></author><author><name sortKey="Caldwell, Jason W" sort="Caldwell, Jason W" uniqKey="Caldwell J" first="Jason W" last="Caldwell">Jason W. Caldwell</name><affiliation wicri:level="2"><nlm:affiliation>Section of Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest University School of Medicine, Winston-Salem, NC, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest University School of Medicine, Winston-Salem, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Huang, Yanping" sort="Huang, Yanping" uniqKey="Huang Y" first="Yanping" last="Huang">Yanping Huang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Burkhardt, Janis K" sort="Burkhardt, Janis K" uniqKey="Burkhardt J" first="Janis K" last="Burkhardt">Janis K. Burkhardt</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Latour, Sylvain" sort="Latour, Sylvain" uniqKey="Latour S" first="Sylvain" last="Latour">Sylvain Latour</name><affiliation wicri:level="3"><nlm:affiliation>Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR 1163, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR 1163, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>University Paris Descartes Sorbonne Paris Cité, Institut des Maladies Génétiques-IMAGINE, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University Paris Descartes Sorbonne Paris Cité, Institut des Maladies Génétiques-IMAGINE, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Chen, Baoyu" sort="Chen, Baoyu" uniqKey="Chen B" first="Baoyu" last="Chen">Baoyu Chen</name><affiliation wicri:level="4"><nlm:affiliation>Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Ames (Iowa)</settlement></placeName><orgName type="university">Université d'État de l'Iowa</orgName></affiliation></author><author><name sortKey="Elghazali, Gehad" sort="Elghazali, Gehad" uniqKey="Elghazali G" first="Gehad" last="Elghazali">Gehad Elghazali</name><affiliation wicri:level="1"><nlm:affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author><author><name sortKey="Rao, V Koneti" sort="Rao, V Koneti" uniqKey="Rao V" first="V Koneti" last="Rao">V Koneti Rao</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Chinn, Ivan K" sort="Chinn, Ivan K" uniqKey="Chinn I" first="Ivan K" last="Chinn">Ivan K. Chinn</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Lenardo, Michael J" sort="Lenardo, Michael J" uniqKey="Lenardo M" first="Michael J" last="Lenardo">Michael J. Lenardo</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. lenardo@nih.gov.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32647003</idno><idno type="pmid">32647003</idno><idno type="doi">10.1126/science.aay5663</idno><idno type="wicri:Area/Main/Corpus">000047</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000047</idno><idno type="wicri:Area/Main/Curation">000047</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000047</idno><idno type="wicri:Area/Main/Exploration">000047</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease.</title><author><name sortKey="Cook, Sarah A" sort="Cook, Sarah A" uniqKey="Cook S" first="Sarah A" last="Cook">Sarah A. Cook</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Comrie, William A" sort="Comrie, William A" uniqKey="Comrie W" first="William A" last="Comrie">William A. Comrie</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Neomics Pharmaceuticals, LLC, Gaithersburg, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neomics Pharmaceuticals, LLC, Gaithersburg, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Poli, M Cecilia" sort="Poli, M Cecilia" uniqKey="Poli M" first="M Cecilia" last="Poli">M Cecilia Poli</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Program of Immunogenetics and Translational Immunology, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile.</nlm:affiliation><country xml:lang="fr">Chili</country><wicri:regionArea>Program of Immunogenetics and Translational Immunology, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Similuk, Morgan" sort="Similuk, Morgan" uniqKey="Similuk M" first="Morgan" last="Similuk">Morgan Similuk</name><affiliation wicri:level="2"><nlm:affiliation>Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Intramural Research, NIAID, NIH, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Oler, Andrew J" sort="Oler, Andrew J" uniqKey="Oler A" first="Andrew J" last="Oler">Andrew J. Oler</name><affiliation wicri:level="2"><nlm:affiliation>Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Faruqi, Aiman J" sort="Faruqi, Aiman J" uniqKey="Faruqi A" first="Aiman J" last="Faruqi">Aiman J. Faruqi</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kuhns, Douglas B" sort="Kuhns, Douglas B" uniqKey="Kuhns D" first="Douglas B" last="Kuhns">Douglas B. Kuhns</name><affiliation wicri:level="2"><nlm:affiliation>Neutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Yang, Sheng" sort="Yang, Sheng" uniqKey="Yang S" first="Sheng" last="Yang">Sheng Yang</name><affiliation wicri:level="4"><nlm:affiliation>Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Ames (Iowa)</settlement></placeName><orgName type="university">Université d'État de l'Iowa</orgName></affiliation></author><author><name sortKey="Vargas Hernandez, Alexander" sort="Vargas Hernandez, Alexander" uniqKey="Vargas Hernandez A" first="Alexander" last="Vargas-Hernández">Alexander Vargas-Hernández</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Carisey, Alexandre F" sort="Carisey, Alexandre F" uniqKey="Carisey A" first="Alexandre F" last="Carisey">Alexandre F. Carisey</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Fournier, Benjamin" sort="Fournier, Benjamin" uniqKey="Fournier B" first="Benjamin" last="Fournier">Benjamin Fournier</name><affiliation wicri:level="3"><nlm:affiliation>Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR 1163, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR 1163, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>University Paris Descartes Sorbonne Paris Cité, Institut des Maladies Génétiques-IMAGINE, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University Paris Descartes Sorbonne Paris Cité, Institut des Maladies Génétiques-IMAGINE, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Anderson, D Eric" sort="Anderson, D Eric" uniqKey="Anderson D" first="D Eric" last="Anderson">D Eric Anderson</name><affiliation wicri:level="2"><nlm:affiliation>Advanced Mass Spectrometry Facility, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Advanced Mass Spectrometry Facility, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Price, Susan" sort="Price, Susan" uniqKey="Price S" first="Susan" last="Price">Susan Price</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Smelkinson, Margery" sort="Smelkinson, Margery" uniqKey="Smelkinson M" first="Margery" last="Smelkinson">Margery Smelkinson</name><affiliation wicri:level="2"><nlm:affiliation>Biological Imaging Section, Research Technologies Branch, NIAID, NIH, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biological Imaging Section, Research Technologies Branch, NIAID, NIH, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Abou Chahla, Wadih" sort="Abou Chahla, Wadih" uniqKey="Abou Chahla W" first="Wadih" last="Abou Chahla">Wadih Abou Chahla</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pediatric Hematology, Jeanne de Flandre Hospital, Centre Hospitalier Universitaire (CHU), Lille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Pediatric Hematology, Jeanne de Flandre Hospital, Centre Hospitalier Universitaire (CHU), Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Forbes, Lisa R" sort="Forbes, Lisa R" uniqKey="Forbes L" first="Lisa R" last="Forbes">Lisa R. Forbes</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Mace, Emily M" sort="Mace, Emily M" uniqKey="Mace E" first="Emily M" last="Mace">Emily M. Mace</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Columbia University Irving Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Cao, Tram N" sort="Cao, Tram N" uniqKey="Cao T" first="Tram N" last="Cao">Tram N. Cao</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Coban Akdemir, Zeynep H" sort="Coban Akdemir, Zeynep H" uniqKey="Coban Akdemir Z" first="Zeynep H" last="Coban-Akdemir">Zeynep H. Coban-Akdemir</name><affiliation wicri:level="2"><nlm:affiliation>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Jhangiani, Shalini N" sort="Jhangiani, Shalini N" uniqKey="Jhangiani S" first="Shalini N" last="Jhangiani">Shalini N. Jhangiani</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Muzny, Donna M" sort="Muzny, Donna M" uniqKey="Muzny D" first="Donna M" last="Muzny">Donna M. Muzny</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Gibbs, Richard A" sort="Gibbs, Richard A" uniqKey="Gibbs R" first="Richard A" last="Gibbs">Richard A. Gibbs</name><affiliation wicri:level="2"><nlm:affiliation>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Lupski, James R" sort="Lupski, James R" uniqKey="Lupski J" first="James R" last="Lupski">James R. Lupski</name><affiliation wicri:level="2"><nlm:affiliation>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Orange, Jordan S" sort="Orange, Jordan S" uniqKey="Orange J" first="Jordan S" last="Orange">Jordan S. Orange</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Columbia University Irving Medical Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Cuvelier, Geoffrey D E" sort="Cuvelier, Geoffrey D E" uniqKey="Cuvelier G" first="Geoffrey D E" last="Cuvelier">Geoffrey D E. Cuvelier</name><affiliation wicri:level="4"><nlm:affiliation>Section of Pediatric Hematology/Oncology/BMT, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Section of Pediatric Hematology/Oncology/BMT, CancerCare Manitoba, University of Manitoba, Winnipeg, MB</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Al Hassani, Moza" sort="Al Hassani, Moza" uniqKey="Al Hassani M" first="Moza" last="Al Hassani">Moza Al Hassani</name><affiliation wicri:level="1"><nlm:affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author><author><name sortKey="Al Kaabi, Nawal" sort="Al Kaabi, Nawal" uniqKey="Al Kaabi N" first="Nawal" last="Al Kaabi">Nawal Al Kaabi</name><affiliation wicri:level="1"><nlm:affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author><author><name sortKey="Al Yafei, Zain" sort="Al Yafei, Zain" uniqKey="Al Yafei Z" first="Zain" last="Al Yafei">Zain Al Yafei</name><affiliation wicri:level="1"><nlm:affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author><author><name sortKey="Jyonouchi, Soma" sort="Jyonouchi, Soma" uniqKey="Jyonouchi S" first="Soma" last="Jyonouchi">Soma Jyonouchi</name><affiliation wicri:level="2"><nlm:affiliation>Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Raje, Nikita" sort="Raje, Nikita" uniqKey="Raje N" first="Nikita" last="Raje">Nikita Raje</name><affiliation wicri:level="2"><nlm:affiliation>Division of Allergy, Immunology, Pulmonary, and Sleep Medicine, Children's Mercy Hospital, Kansas City, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Allergy, Immunology, Pulmonary, and Sleep Medicine, Children's Mercy Hospital, Kansas City, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Internal Medicine and Pediatrics, University of Missouri Kansas City, Kansas City, MO, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine and Pediatrics, University of Missouri Kansas City, Kansas City, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region></placeName></affiliation></author><author><name sortKey="Caldwell, Jason W" sort="Caldwell, Jason W" uniqKey="Caldwell J" first="Jason W" last="Caldwell">Jason W. Caldwell</name><affiliation wicri:level="2"><nlm:affiliation>Section of Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest University School of Medicine, Winston-Salem, NC, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest University School of Medicine, Winston-Salem, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Huang, Yanping" sort="Huang, Yanping" uniqKey="Huang Y" first="Yanping" last="Huang">Yanping Huang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Burkhardt, Janis K" sort="Burkhardt, Janis K" uniqKey="Burkhardt J" first="Janis K" last="Burkhardt">Janis K. Burkhardt</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Latour, Sylvain" sort="Latour, Sylvain" uniqKey="Latour S" first="Sylvain" last="Latour">Sylvain Latour</name><affiliation wicri:level="3"><nlm:affiliation>Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR 1163, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR 1163, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>University Paris Descartes Sorbonne Paris Cité, Institut des Maladies Génétiques-IMAGINE, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University Paris Descartes Sorbonne Paris Cité, Institut des Maladies Génétiques-IMAGINE, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Chen, Baoyu" sort="Chen, Baoyu" uniqKey="Chen B" first="Baoyu" last="Chen">Baoyu Chen</name><affiliation wicri:level="4"><nlm:affiliation>Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Ames (Iowa)</settlement></placeName><orgName type="university">Université d'État de l'Iowa</orgName></affiliation></author><author><name sortKey="Elghazali, Gehad" sort="Elghazali, Gehad" uniqKey="Elghazali G" first="Gehad" last="Elghazali">Gehad Elghazali</name><affiliation wicri:level="1"><nlm:affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author><author><name sortKey="Rao, V Koneti" sort="Rao, V Koneti" uniqKey="Rao V" first="V Koneti" last="Rao">V Koneti Rao</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Chinn, Ivan K" sort="Chinn, Ivan K" uniqKey="Chinn I" first="Ivan K" last="Chinn">Ivan K. Chinn</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Lenardo, Michael J" sort="Lenardo, Michael J" uniqKey="Lenardo M" first="Michael J" last="Lenardo">Michael J. Lenardo</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. lenardo@nih.gov.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j">Science (New York, N.Y.)</title><idno type="eISSN">1095-9203</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ADP-Ribosylation Factor 1 (metabolism)</term><term>Actins (metabolism)</term><term>CD4-Positive T-Lymphocytes (immunology)</term><term>Cell Proliferation (MeSH)</term><term>Cytokines (biosynthesis)</term><term>Humans (MeSH)</term><term>Immunologic Deficiency Syndromes (genetics)</term><term>Immunologic Deficiency Syndromes (immunology)</term><term>Lymphoproliferative Disorders (genetics)</term><term>Lymphoproliferative Disorders (immunology)</term><term>Mechanistic Target of Rapamycin Complex 2 (metabolism)</term><term>Membrane Proteins (genetics)</term><term>Membrane Proteins (physiology)</term><term>Pedigree (MeSH)</term><term>Phosphorylation (MeSH)</term><term>Wiskott-Aldrich Syndrome Protein Family (chemistry)</term><term>Wiskott-Aldrich Syndrome Protein Family (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Actines (métabolisme)</term><term>Complexe-2 cible mécanistique de la rapamycine (métabolisme)</term><term>Cytokines (biosynthèse)</term><term>Déficits immunitaires (génétique)</term><term>Déficits immunitaires (immunologie)</term><term>Facteur-1 d'ADP-ribosylation (métabolisme)</term><term>Famille de protéines du syndrome de Wiskott-Aldrich (composition chimique)</term><term>Famille de protéines du syndrome de Wiskott-Aldrich (métabolisme)</term><term>Humains (MeSH)</term><term>Lymphocytes T CD4+ (immunologie)</term><term>Pedigree (MeSH)</term><term>Phosphorylation (MeSH)</term><term>Prolifération cellulaire (MeSH)</term><term>Protéines membranaires (génétique)</term><term>Protéines membranaires (physiologie)</term><term>Syndromes lymphoprolifératifs (génétique)</term><term>Syndromes lymphoprolifératifs (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cytokines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Wiskott-Aldrich Syndrome Protein Family</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>ADP-Ribosylation Factor 1</term><term>Actins</term><term>Mechanistic Target of Rapamycin Complex 2</term><term>Wiskott-Aldrich Syndrome Protein Family</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Cytokines</term></keywords><keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Famille de protéines du syndrome de Wiskott-Aldrich</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Immunologic Deficiency Syndromes</term><term>Lymphoproliferative Disorders</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Déficits immunitaires</term><term>Protéines membranaires</term><term>Syndromes lymphoprolifératifs</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Déficits immunitaires</term><term>Lymphocytes T CD4+</term><term>Syndromes lymphoprolifératifs</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>Immunologic Deficiency Syndromes</term><term>Lymphoproliferative Disorders</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Actines</term><term>Complexe-2 cible mécanistique de la rapamycine</term><term>Facteur-1 d'ADP-ribosylation</term><term>Famille de protéines du syndrome de Wiskott-Aldrich</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Protéines membranaires</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Membrane Proteins</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Proliferation</term><term>Humans</term><term>Pedigree</term><term>Phosphorylation</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Pedigree</term><term>Phosphorylation</term><term>Prolifération cellulaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Immunodeficiency often coincides with hyperactive immune disorders such as autoimmunity, lymphoproliferation, or atopy, but this coincidence is rarely understood on a molecular level. We describe five patients from four families with immunodeficiency coupled with atopy, lymphoproliferation, and cytokine overproduction harboring mutations in <i>NCKAP1L</i>, which encodes the hematopoietic-specific HEM1 protein. These mutations cause the loss of the HEM1 protein and the WAVE regulatory complex (WRC) or disrupt binding to the WRC regulator, Arf1, thereby impairing actin polymerization, synapse formation, and immune cell migration. Diminished cortical actin networks caused by WRC loss led to uncontrolled cytokine release and immune hyperresponsiveness. HEM1 loss also blocked mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, T cell proliferation, and selected effector functions, leading to immunodeficiency. Thus, the evolutionarily conserved HEM1 protein simultaneously regulates filamentous actin (F-actin) and mTORC2 signaling to achieve equipoise in immune responses.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32647003</PMID><DateCompleted><Year>2020</Year><Month>07</Month><Day>16</Day></DateCompleted><DateRevised><Year>2020</Year><Month>07</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1095-9203</ISSN><JournalIssue CitedMedium="Internet"><Volume>369</Volume><Issue>6500</Issue><PubDate><Year>2020</Year><Month>07</Month><Day>10</Day></PubDate></JournalIssue><Title>Science (New York, N.Y.)</Title><ISOAbbreviation>Science</ISOAbbreviation></Journal><ArticleTitle>HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease.</ArticleTitle><Pagination><MedlinePgn>202-207</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1126/science.aay5663</ELocationID><Abstract><AbstractText>Immunodeficiency often coincides with hyperactive immune disorders such as autoimmunity, lymphoproliferation, or atopy, but this coincidence is rarely understood on a molecular level. We describe five patients from four families with immunodeficiency coupled with atopy, lymphoproliferation, and cytokine overproduction harboring mutations in <i>NCKAP1L</i>, which encodes the hematopoietic-specific HEM1 protein. These mutations cause the loss of the HEM1 protein and the WAVE regulatory complex (WRC) or disrupt binding to the WRC regulator, Arf1, thereby impairing actin polymerization, synapse formation, and immune cell migration. Diminished cortical actin networks caused by WRC loss led to uncontrolled cytokine release and immune hyperresponsiveness. HEM1 loss also blocked mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, T cell proliferation, and selected effector functions, leading to immunodeficiency. Thus, the evolutionarily conserved HEM1 protein simultaneously regulates filamentous actin (F-actin) and mTORC2 signaling to achieve equipoise in immune responses.</AbstractText><CopyrightInformation>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Cook</LastName><ForeName>Sarah A</ForeName><Initials>SA</Initials><Identifier Source="ORCID">0000-0002-2923-4009</Identifier><AffiliationInfo><Affiliation>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Comrie</LastName><ForeName>William A</ForeName><Initials>WA</Initials><Identifier Source="ORCID">0000-0003-1173-1127</Identifier><AffiliationInfo><Affiliation>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Neomics Pharmaceuticals, LLC, Gaithersburg, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Poli</LastName><ForeName>M Cecilia</ForeName><Initials>MC</Initials><Identifier Source="ORCID">0000-0001-6817-0573</Identifier><AffiliationInfo><Affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Program of Immunogenetics and Translational Immunology, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Similuk</LastName><ForeName>Morgan</ForeName><Initials>M</Initials><Identifier Source="ORCID">0000-0002-0403-2689</Identifier><AffiliationInfo><Affiliation>Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oler</LastName><ForeName>Andrew J</ForeName><Initials>AJ</Initials><Identifier Source="ORCID">0000-0002-6310-0434</Identifier><AffiliationInfo><Affiliation>Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Faruqi</LastName><ForeName>Aiman J</ForeName><Initials>AJ</Initials><Identifier Source="ORCID">0000-0002-4421-3767</Identifier><AffiliationInfo><Affiliation>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kuhns</LastName><ForeName>Douglas B</ForeName><Initials>DB</Initials><Identifier Source="ORCID">0000-0002-9971-0760</Identifier><AffiliationInfo><Affiliation>Neutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Sheng</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0002-0321-3728</Identifier><AffiliationInfo><Affiliation>Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vargas-Hernández</LastName><ForeName>Alexander</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carisey</LastName><ForeName>Alexandre F</ForeName><Initials>AF</Initials><Identifier Source="ORCID">0000-0003-1326-2205</Identifier><AffiliationInfo><Affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fournier</LastName><ForeName>Benjamin</ForeName><Initials>B</Initials><Identifier Source="ORCID">0000-0002-4189-996X</Identifier><AffiliationInfo><Affiliation>Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR 1163, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University Paris Descartes Sorbonne Paris Cité, Institut des Maladies Génétiques-IMAGINE, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anderson</LastName><ForeName>D Eric</ForeName><Initials>DE</Initials><Identifier Source="ORCID">0000-0002-6838-0201</Identifier><AffiliationInfo><Affiliation>Advanced Mass Spectrometry Facility, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Price</LastName><ForeName>Susan</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0002-1004-8441</Identifier><AffiliationInfo><Affiliation>Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smelkinson</LastName><ForeName>Margery</ForeName><Initials>M</Initials><Identifier Source="ORCID">0000-0001-7777-5574</Identifier><AffiliationInfo><Affiliation>Biological Imaging Section, Research Technologies Branch, NIAID, NIH, Bethesda, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Abou Chahla</LastName><ForeName>Wadih</ForeName><Initials>W</Initials><Identifier Source="ORCID">0000-0002-8170-0951</Identifier><AffiliationInfo><Affiliation>Department of Pediatric Hematology, Jeanne de Flandre Hospital, Centre Hospitalier Universitaire (CHU), Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Forbes</LastName><ForeName>Lisa R</ForeName><Initials>LR</Initials><Identifier Source="ORCID">0000-0001-9402-1934</Identifier><AffiliationInfo><Affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mace</LastName><ForeName>Emily M</ForeName><Initials>EM</Initials><Identifier Source="ORCID">0000-0003-0226-7393</Identifier><AffiliationInfo><Affiliation>Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cao</LastName><ForeName>Tram N</ForeName><Initials>TN</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coban-Akdemir</LastName><ForeName>Zeynep H</ForeName><Initials>ZH</Initials><Identifier Source="ORCID">0000-0001-9928-9032</Identifier><AffiliationInfo><Affiliation>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jhangiani</LastName><ForeName>Shalini N</ForeName><Initials>SN</Initials><Identifier Source="ORCID">0000-0002-6674-0074</Identifier><AffiliationInfo><Affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Muzny</LastName><ForeName>Donna M</ForeName><Initials>DM</Initials><Identifier Source="ORCID">0000-0002-3055-0359</Identifier><AffiliationInfo><Affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gibbs</LastName><ForeName>Richard A</ForeName><Initials>RA</Initials><Identifier Source="ORCID">0000-0002-1356-5698</Identifier><AffiliationInfo><Affiliation>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lupski</LastName><ForeName>James R</ForeName><Initials>JR</Initials><Identifier Source="ORCID">0000-0001-9907-9246</Identifier><AffiliationInfo><Affiliation>Baylor-Hopkins Center for Mendelian Genomics, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Orange</LastName><ForeName>Jordan S</ForeName><Initials>JS</Initials><Identifier Source="ORCID">0000-0001-7117-7725</Identifier><AffiliationInfo><Affiliation>Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cuvelier</LastName><ForeName>Geoffrey D E</ForeName><Initials>GDE</Initials><Identifier Source="ORCID">0000-0003-4493-8757</Identifier><AffiliationInfo><Affiliation>Section of Pediatric Hematology/Oncology/BMT, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Al Hassani</LastName><ForeName>Moza</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Al Kaabi</LastName><ForeName>Nawal</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Al Yafei</LastName><ForeName>Zain</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jyonouchi</LastName><ForeName>Soma</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Raje</LastName><ForeName>Nikita</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Division of Allergy, Immunology, Pulmonary, and Sleep Medicine, Children's Mercy Hospital, Kansas City, MO, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Internal Medicine and Pediatrics, University of Missouri Kansas City, Kansas City, MO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Caldwell</LastName><ForeName>Jason W</ForeName><Initials>JW</Initials><Identifier Source="ORCID">0000-0003-4617-8982</Identifier><AffiliationInfo><Affiliation>Section of Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest University School of Medicine, Winston-Salem, NC, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Yanping</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Burkhardt</LastName><ForeName>Janis K</ForeName><Initials>JK</Initials><Identifier Source="ORCID">0000-0002-8176-1375</Identifier><AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Latour</LastName><ForeName>Sylvain</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0001-8238-4391</Identifier><AffiliationInfo><Affiliation>Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR 1163, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University Paris Descartes Sorbonne Paris Cité, Institut des Maladies Génétiques-IMAGINE, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Baoyu</ForeName><Initials>B</Initials><Identifier Source="ORCID">0000-0002-6366-159X</Identifier><AffiliationInfo><Affiliation>Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>ElGhazali</LastName><ForeName>Gehad</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Sheikh Khalifa Medical City, Abu Dhabi Healthcare Company (SEHA), Abu Dhabi, United Arab Emirates.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rao</LastName><ForeName>V Koneti</ForeName><Initials>VK</Initials><Identifier Source="ORCID">0000-0002-7881-6902</Identifier><AffiliationInfo><Affiliation>Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chinn</LastName><ForeName>Ivan K</ForeName><Initials>IK</Initials><Identifier Source="ORCID">0000-0001-5684-5457</Identifier><AffiliationInfo><Affiliation>Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Section of Pediatric Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lenardo</LastName><ForeName>Michael J</ForeName><Initials>MJ</Initials><Identifier Source="ORCID">0000-0003-1584-468X</Identifier><AffiliationInfo><Affiliation>Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. lenardo@nih.gov.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI120989</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R35 GM128786</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UM1 HG006542</GrantID><Acronym>HG</Acronym><Agency>NHGRI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Science</MedlineTA><NlmUniqueID>0404511</NlmUniqueID><ISSNLinking>0036-8075</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000199">Actins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016207">Cytokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008565">Membrane Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C114864">WASF1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C120152">WASF2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C120153">WASF3 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051300">Wiskott-Aldrich Syndrome Protein Family</NameOfSubstance></Chemical><Chemical><RegistryNumber>144351-15-5</RegistryNumber><NameOfSubstance UI="C095128">NCKAP1L protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076225">Mechanistic Target of Rapamycin Complex 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.6.5.2</RegistryNumber><NameOfSubstance UI="D020823">ADP-Ribosylation Factor 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.6.5.2</RegistryNumber><NameOfSubstance UI="C000655468">ARF1 protein, human</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D020823" MajorTopicYN="N">ADP-Ribosylation Factor 1</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000199" MajorTopicYN="N">Actins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007153" MajorTopicYN="N">Immunologic Deficiency Syndromes</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008232" MajorTopicYN="N">Lymphoproliferative Disorders</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000076225" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008565" MajorTopicYN="N">Membrane Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010375" MajorTopicYN="N">Pedigree</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051300" MajorTopicYN="N">Wiskott-Aldrich Syndrome Protein Family</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>06</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>01</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>05</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>7</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>7</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>7</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32647003</ArticleId><ArticleId IdType="pii">369/6500/202</ArticleId><ArticleId IdType="doi">10.1126/science.aay5663</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li><li>Chili</li><li>France</li><li>Émirats arabes unis</li><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Hauts-de-France</li><li>Iowa</li><li>Manitoba</li><li>Maryland</li><li>Missouri (État)</li><li>Nord-Pas-de-Calais</li><li>Pennsylvanie</li><li>Texas</li><li>État de New York</li><li>Île-de-France</li></region><settlement><li>Ames (Iowa)</li><li>Lille</li><li>Paris</li><li>Winnipeg</li></settlement><orgName><li>Université d'État de l'Iowa</li><li>Université du Manitoba</li></orgName></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Cook, Sarah A" sort="Cook, Sarah A" uniqKey="Cook S" first="Sarah A" last="Cook">Sarah A. Cook</name></region><name sortKey="Anderson, D Eric" sort="Anderson, D Eric" uniqKey="Anderson D" first="D Eric" last="Anderson">D Eric Anderson</name><name sortKey="Burkhardt, Janis K" sort="Burkhardt, Janis K" uniqKey="Burkhardt J" first="Janis K" last="Burkhardt">Janis K. Burkhardt</name><name sortKey="Caldwell, Jason W" sort="Caldwell, Jason W" uniqKey="Caldwell J" first="Jason W" last="Caldwell">Jason W. Caldwell</name><name sortKey="Cao, Tram N" sort="Cao, Tram N" uniqKey="Cao T" first="Tram N" last="Cao">Tram N. Cao</name><name sortKey="Cao, Tram N" sort="Cao, Tram N" uniqKey="Cao T" first="Tram N" last="Cao">Tram N. Cao</name><name sortKey="Carisey, Alexandre F" sort="Carisey, Alexandre F" uniqKey="Carisey A" first="Alexandre F" last="Carisey">Alexandre F. Carisey</name><name sortKey="Carisey, Alexandre F" sort="Carisey, Alexandre F" uniqKey="Carisey A" first="Alexandre F" last="Carisey">Alexandre F. Carisey</name><name sortKey="Chen, Baoyu" sort="Chen, Baoyu" uniqKey="Chen B" first="Baoyu" last="Chen">Baoyu Chen</name><name sortKey="Chinn, Ivan K" sort="Chinn, Ivan K" uniqKey="Chinn I" first="Ivan K" last="Chinn">Ivan K. Chinn</name><name sortKey="Chinn, Ivan K" sort="Chinn, Ivan K" uniqKey="Chinn I" first="Ivan K" last="Chinn">Ivan K. Chinn</name><name sortKey="Coban Akdemir, Zeynep H" sort="Coban Akdemir, Zeynep H" uniqKey="Coban Akdemir Z" first="Zeynep H" last="Coban-Akdemir">Zeynep H. Coban-Akdemir</name><name sortKey="Coban Akdemir, Zeynep H" sort="Coban Akdemir, Zeynep H" uniqKey="Coban Akdemir Z" first="Zeynep H" last="Coban-Akdemir">Zeynep H. Coban-Akdemir</name><name sortKey="Comrie, William A" sort="Comrie, William A" uniqKey="Comrie W" first="William A" last="Comrie">William A. Comrie</name><name sortKey="Comrie, William A" sort="Comrie, William A" uniqKey="Comrie W" first="William A" last="Comrie">William A. Comrie</name><name sortKey="Faruqi, Aiman J" sort="Faruqi, Aiman J" uniqKey="Faruqi A" first="Aiman J" last="Faruqi">Aiman J. Faruqi</name><name sortKey="Forbes, Lisa R" sort="Forbes, Lisa R" uniqKey="Forbes L" first="Lisa R" last="Forbes">Lisa R. Forbes</name><name sortKey="Forbes, Lisa R" sort="Forbes, Lisa R" uniqKey="Forbes L" first="Lisa R" last="Forbes">Lisa R. Forbes</name><name sortKey="Gibbs, Richard A" sort="Gibbs, Richard A" uniqKey="Gibbs R" first="Richard A" last="Gibbs">Richard A. Gibbs</name><name sortKey="Gibbs, Richard A" sort="Gibbs, Richard A" uniqKey="Gibbs R" first="Richard A" last="Gibbs">Richard A. Gibbs</name><name sortKey="Gibbs, Richard A" sort="Gibbs, Richard A" uniqKey="Gibbs R" first="Richard A" last="Gibbs">Richard A. Gibbs</name><name sortKey="Huang, Yanping" sort="Huang, Yanping" uniqKey="Huang Y" first="Yanping" last="Huang">Yanping Huang</name><name sortKey="Huang, Yanping" sort="Huang, Yanping" uniqKey="Huang Y" first="Yanping" last="Huang">Yanping Huang</name><name sortKey="Jhangiani, Shalini N" sort="Jhangiani, Shalini N" uniqKey="Jhangiani S" first="Shalini N" last="Jhangiani">Shalini N. Jhangiani</name><name sortKey="Jhangiani, Shalini N" sort="Jhangiani, Shalini N" uniqKey="Jhangiani S" first="Shalini N" last="Jhangiani">Shalini N. Jhangiani</name><name sortKey="Jyonouchi, Soma" sort="Jyonouchi, Soma" uniqKey="Jyonouchi S" first="Soma" last="Jyonouchi">Soma Jyonouchi</name><name sortKey="Jyonouchi, Soma" sort="Jyonouchi, Soma" uniqKey="Jyonouchi S" first="Soma" last="Jyonouchi">Soma Jyonouchi</name><name sortKey="Kuhns, Douglas B" sort="Kuhns, Douglas B" uniqKey="Kuhns D" first="Douglas B" last="Kuhns">Douglas B. Kuhns</name><name sortKey="Lenardo, Michael J" sort="Lenardo, Michael J" uniqKey="Lenardo M" first="Michael J" last="Lenardo">Michael J. Lenardo</name><name sortKey="Lupski, James R" sort="Lupski, James R" uniqKey="Lupski J" first="James R" last="Lupski">James R. Lupski</name><name sortKey="Lupski, James R" sort="Lupski, James R" uniqKey="Lupski J" first="James R" last="Lupski">James R. Lupski</name><name sortKey="Lupski, James R" sort="Lupski, James R" uniqKey="Lupski J" first="James R" last="Lupski">James R. Lupski</name><name sortKey="Mace, Emily M" sort="Mace, Emily M" uniqKey="Mace E" first="Emily M" last="Mace">Emily M. Mace</name><name sortKey="Muzny, Donna M" sort="Muzny, Donna M" uniqKey="Muzny D" first="Donna M" last="Muzny">Donna M. Muzny</name><name sortKey="Muzny, Donna M" sort="Muzny, Donna M" uniqKey="Muzny D" first="Donna M" last="Muzny">Donna M. Muzny</name><name sortKey="Oler, Andrew J" sort="Oler, Andrew J" uniqKey="Oler A" first="Andrew J" last="Oler">Andrew J. Oler</name><name sortKey="Orange, Jordan S" sort="Orange, Jordan S" uniqKey="Orange J" first="Jordan S" last="Orange">Jordan S. Orange</name><name sortKey="Poli, M Cecilia" sort="Poli, M Cecilia" uniqKey="Poli M" first="M Cecilia" last="Poli">M Cecilia Poli</name><name sortKey="Poli, M Cecilia" sort="Poli, M Cecilia" uniqKey="Poli M" first="M Cecilia" last="Poli">M Cecilia Poli</name><name sortKey="Price, Susan" sort="Price, Susan" uniqKey="Price S" first="Susan" last="Price">Susan Price</name><name sortKey="Raje, Nikita" sort="Raje, Nikita" uniqKey="Raje N" first="Nikita" last="Raje">Nikita Raje</name><name sortKey="Raje, Nikita" sort="Raje, Nikita" uniqKey="Raje N" first="Nikita" last="Raje">Nikita Raje</name><name sortKey="Rao, V Koneti" sort="Rao, V Koneti" uniqKey="Rao V" first="V Koneti" last="Rao">V Koneti Rao</name><name sortKey="Similuk, Morgan" sort="Similuk, Morgan" uniqKey="Similuk M" first="Morgan" last="Similuk">Morgan Similuk</name><name sortKey="Smelkinson, Margery" sort="Smelkinson, Margery" uniqKey="Smelkinson M" first="Margery" last="Smelkinson">Margery Smelkinson</name><name sortKey="Vargas Hernandez, Alexander" sort="Vargas Hernandez, Alexander" uniqKey="Vargas Hernandez A" first="Alexander" last="Vargas-Hernández">Alexander Vargas-Hernández</name><name sortKey="Vargas Hernandez, Alexander" sort="Vargas Hernandez, Alexander" uniqKey="Vargas Hernandez A" first="Alexander" last="Vargas-Hernández">Alexander Vargas-Hernández</name><name sortKey="Yang, Sheng" sort="Yang, Sheng" uniqKey="Yang S" first="Sheng" last="Yang">Sheng Yang</name></country><country name="Chili"><noRegion><name sortKey="Poli, M Cecilia" sort="Poli, M Cecilia" uniqKey="Poli M" first="M Cecilia" last="Poli">M Cecilia Poli</name></noRegion></country><country name="France"><region name="Île-de-France"><name sortKey="Fournier, Benjamin" sort="Fournier, Benjamin" uniqKey="Fournier B" first="Benjamin" last="Fournier">Benjamin Fournier</name></region><name sortKey="Abou Chahla, Wadih" sort="Abou Chahla, Wadih" uniqKey="Abou Chahla W" first="Wadih" last="Abou Chahla">Wadih Abou Chahla</name><name sortKey="Fournier, Benjamin" sort="Fournier, Benjamin" uniqKey="Fournier B" first="Benjamin" last="Fournier">Benjamin Fournier</name><name sortKey="Latour, Sylvain" sort="Latour, Sylvain" uniqKey="Latour S" first="Sylvain" last="Latour">Sylvain Latour</name><name sortKey="Latour, Sylvain" sort="Latour, Sylvain" uniqKey="Latour S" first="Sylvain" last="Latour">Sylvain Latour</name></country><country name="Canada"><region name="Manitoba"><name sortKey="Cuvelier, Geoffrey D E" sort="Cuvelier, Geoffrey D E" uniqKey="Cuvelier G" first="Geoffrey D E" last="Cuvelier">Geoffrey D E. Cuvelier</name></region></country><country name="Émirats arabes unis"><noRegion><name sortKey="Al Hassani, Moza" sort="Al Hassani, Moza" uniqKey="Al Hassani M" first="Moza" last="Al Hassani">Moza Al Hassani</name></noRegion><name sortKey="Al Kaabi, Nawal" sort="Al Kaabi, Nawal" uniqKey="Al Kaabi N" first="Nawal" last="Al Kaabi">Nawal Al Kaabi</name><name sortKey="Al Yafei, Zain" sort="Al Yafei, Zain" uniqKey="Al Yafei Z" first="Zain" last="Al Yafei">Zain Al Yafei</name><name sortKey="Elghazali, Gehad" sort="Elghazali, Gehad" uniqKey="Elghazali G" first="Gehad" last="Elghazali">Gehad Elghazali</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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