LymphedemaV1, Main, Merge, bibRecord, 004200

Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature

Identifieur interne : 004200 ( Main/Merge ); précédent : 004199; suivant : 004201

Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature

Auteurs : Jan Kazenwadel [Australie] ; Genevieve A. Secker [Australie] ; Yajuan J. Liu [États-Unis] ; Jill A. Rosenfeld [États-Unis] ; Robert S. Wildin [États-Unis] ; Jennifer Cuellar-Rodriguez [États-Unis] ; Amy P. Hsu [États-Unis] ; Sarah Dyack ; Conrad V. Fernandez ; Chan-Eng Chong [Australie] ; Milena Babic [Australie] ; Peter G. Bardy [Australie] ; Akiko Shimamura [États-Unis] ; Michael Y. Zhang [États-Unis] ; Tom Walsh [États-Unis] ; Steven M. Holland [États-Unis] ; Dennis D. Hickstein [États-Unis] ; Marshall S. Horwitz [États-Unis] ; Christopher N. Hahn [Australie] ; Hamish S. Scott [Australie] ; Natasha L. Harvey [Australie]

Source :

Blood [ 0006-4971 ] ; 2012.

RBID : PMC:3277359

Descripteurs français

KwdFr :
- Adolescent, Adulte, Animaux, Cellules cultivées, Enfant, Facteur de transcription GATA-2 (génétique), Facteur de transcription GATA-2 (métabolisme), Facteur de transcription GATA-2 (physiologie), Femelle, Humains, Jeune adulte, Leucémie aigüe myéloïde (génétique), Lymphangiogenèse (génétique), Lymphoedème (), Lymphoedème (génétique), Monocytes (anatomopathologie), Mutation germinale (physiologie), Mâle, Nouveau-né, Souris, Souris de lignée C57BL, Souris transgéniques, Syndrome, Syndromes myélodysplasiques (génétique), Vaisseaux lymphatiques (métabolisme).
MESH :
- anatomopathologie : Monocytes.
- génétique : Facteur de transcription GATA-2, Leucémie aigüe myéloïde, Lymphangiogenèse, Lymphoedème, Syndromes myélodysplasiques.
- métabolisme : Facteur de transcription GATA-2, Vaisseaux lymphatiques.
- physiologie : Facteur de transcription GATA-2, Mutation germinale.
- Adolescent, Adulte, Animaux, Cellules cultivées, Enfant, Femelle, Humains, Jeune adulte, Lymphoedème, Mâle, Nouveau-né, Souris, Souris de lignée C57BL, Souris transgéniques, Syndrome.

English descriptors

KwdEn :
- Adolescent, Adult, Animals, Cells, Cultured, Child, Female, GATA2 Transcription Factor (genetics), GATA2 Transcription Factor (metabolism), GATA2 Transcription Factor (physiology), Germ-Line Mutation (physiology), Humans, Infant, Newborn, Leukemia, Myeloid, Acute (genetics), Lymphangiogenesis (genetics), Lymphatic Vessels (metabolism), Lymphedema (congenital), Lymphedema (genetics), Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Monocytes (pathology), Myelodysplastic Syndromes (genetics), Syndrome, Young Adult.
MESH :
- chemical , genetics : GATA2 Transcription Factor.
- chemical , metabolism : GATA2 Transcription Factor.
- chemical , physiology : GATA2 Transcription Factor.
- congenital : Lymphedema.
- genetics : Leukemia, Myeloid, Acute, Lymphangiogenesis, Lymphedema, Myelodysplastic Syndromes.
- metabolism : Lymphatic Vessels.
- pathology : Monocytes.
- physiology : Germ-Line Mutation.
- Adolescent, Adult, Animals, Cells, Cultured, Child, Female, Humans, Infant, Newborn, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Syndrome, Young Adult.

Abstract

Recent work has established that heterozygous germline GATA2 mutations predispose carriers to familial myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), “MonoMAC” syndrome, and DCML deficiency. Here, we describe a previously unreported MDS family carrying a missense GATA2 mutation (p.Thr354Met), one patient with MDS/AML carrying a frameshift GATA2 mutation (p.Leu332Thrfs*53), another with MDS harboring a GATA2 splice site mutation, and 3 patients exhibiting MDS or MDS/AML who have large deletions encompassing the GATA2 locus. Intriguingly, 2 MDS/AML or “MonoMAC” syndrome patients with GATA2 deletions and one with a frameshift mutation also have primary lymphedema. Primary lymphedema occurs as a result of aberrations in the development and/or function of lymphatic vessels, spurring us to investigate whether GATA2 plays a role in the lymphatic vasculature. We demonstrate here that GATA2 protein is present at high levels in lymphatic vessel valves and that GATA2 controls the expression of genes important for programming lymphatic valve development. Our data expand the phenotypes associated with germline GATA2 mutations to include predisposition to primary lymphedema and suggest that complete haploinsufficiency or loss of function of GATA2, rather than missense mutations, is the key predisposing factor for lymphedema onset. Moreover, we reveal a crucial role for GATA2 in lymphatic vascular development.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277359

DOI: 10.1182/blood-2011-08-374363
PubMed: 22147895
PubMed Central: 3277359

Links to Exploration step

PMC:3277359

Le document en format XML

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 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature</title>
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<author><name sortKey="Chong, Chan Eng" sort="Chong, Chan Eng" uniqKey="Chong C" first="Chan-Eng" last="Chong">Chan-Eng Chong</name>
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<author><name sortKey="Harvey, Natasha L" sort="Harvey, Natasha L" uniqKey="Harvey N" first="Natasha L." last="Harvey">Natasha L. Harvey</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff9">School of Medicine, University of Adelaide, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medicine, University of Adelaide, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Loss-of-function germline <italic>GATA2</italic>
 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature</title>
<author><name sortKey="Kazenwadel, Jan" sort="Kazenwadel, Jan" uniqKey="Kazenwadel J" first="Jan" last="Kazenwadel">Jan Kazenwadel</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
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<author><name sortKey="Secker, Genevieve A" sort="Secker, Genevieve A" uniqKey="Secker G" first="Genevieve A." last="Secker">Genevieve A. Secker</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
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</author>
<author><name sortKey="Liu, Yajuan J" sort="Liu, Yajuan J" uniqKey="Liu Y" first="Yajuan J." last="Liu">Yajuan J. Liu</name>
<affiliation wicri:level="2"><nlm:aff id="aff2">Department of Pathology, University of Washington School of Medicine, Seattle, WA;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Pathology, University of Washington School of Medicine, Seattle</wicri:cityArea>
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<author><name sortKey="Rosenfeld, Jill A" sort="Rosenfeld, Jill A" uniqKey="Rosenfeld J" first="Jill A." last="Rosenfeld">Jill A. Rosenfeld</name>
<affiliation wicri:level="2"><nlm:aff id="aff3">Signature Genomics, PerkinElmer, Spokane, WA;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Signature Genomics, PerkinElmer, Spokane</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Wildin, Robert S" sort="Wildin, Robert S" uniqKey="Wildin R" first="Robert S." last="Wildin">Robert S. Wildin</name>
<affiliation wicri:level="2"><nlm:aff id="aff4">St Luke's Children's Hospital, Pediatric Genetics, and State of Idaho Genetics Program, Department of Health and Welfare, Boise, ID;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Idaho</region>
</placeName>
<wicri:cityArea>St Luke's Children's Hospital, Pediatric Genetics, and State of Idaho Genetics Program, Department of Health and Welfare, Boise</wicri:cityArea>
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<author><name sortKey="Cuellar Rodriguez, Jennifer" sort="Cuellar Rodriguez, Jennifer" uniqKey="Cuellar Rodriguez J" first="Jennifer" last="Cuellar-Rodriguez">Jennifer Cuellar-Rodriguez</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hsu, Amy P" sort="Hsu, Amy P" uniqKey="Hsu A" first="Amy P." last="Hsu">Amy P. Hsu</name>
<affiliation wicri:level="2"><nlm:aff id="aff5">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Dyack, Sarah" sort="Dyack, Sarah" uniqKey="Dyack S" first="Sarah" last="Dyack">Sarah Dyack</name>
<affiliation><nlm:aff id="aff6">Department of Pediatrics, Maritime Medical Genetics Service, IWK Health Centre and Dalhousie University, Halifax, NS;</nlm:aff>
<wicri:noCountry code="subfield">NS</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Fernandez, Conrad V" sort="Fernandez, Conrad V" uniqKey="Fernandez C" first="Conrad V." last="Fernandez">Conrad V. Fernandez</name>
<affiliation><nlm:aff id="aff7">Departments of Pediatrics and Bioethics, IWK Health Centre and Dalhousie University, Halifax, NS;</nlm:aff>
<wicri:noCountry code="subfield">NS</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Chong, Chan Eng" sort="Chong, Chan Eng" uniqKey="Chong C" first="Chan-Eng" last="Chong">Chan-Eng Chong</name>
<affiliation wicri:level="1"><nlm:aff id="aff8">Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff9">School of Medicine, University of Adelaide, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medicine, University of Adelaide, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Babic, Milena" sort="Babic, Milena" uniqKey="Babic M" first="Milena" last="Babic">Milena Babic</name>
<affiliation wicri:level="1"><nlm:aff id="aff8">Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bardy, Peter G" sort="Bardy, Peter G" uniqKey="Bardy P" first="Peter G." last="Bardy">Peter G. Bardy</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Shimamura, Akiko" sort="Shimamura, Akiko" uniqKey="Shimamura A" first="Akiko" last="Shimamura">Akiko Shimamura</name>
<affiliation wicri:level="2"><nlm:aff id="aff10">Fred Hutchinson Cancer Research Center, Seattle, WA;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff11">Seattle Children's Hospital, Seattle, WA;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Seattle Children's Hospital, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Zhang, Michael Y" sort="Zhang, Michael Y" uniqKey="Zhang M" first="Michael Y." last="Zhang">Michael Y. Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="aff10">Fred Hutchinson Cancer Research Center, Seattle, WA;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff12">Department of Genome Sciences and Department of Medicine, University of Washington, Seattle, WA;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Genome Sciences and Department of Medicine, University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Walsh, Tom" sort="Walsh, Tom" uniqKey="Walsh T" first="Tom" last="Walsh">Tom Walsh</name>
<affiliation wicri:level="2"><nlm:aff id="aff12">Department of Genome Sciences and Department of Medicine, University of Washington, Seattle, WA;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Genome Sciences and Department of Medicine, University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Holland, Steven M" sort="Holland, Steven M" uniqKey="Holland S" first="Steven M." last="Holland">Steven M. Holland</name>
<affiliation wicri:level="2"><nlm:aff id="aff5">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hickstein, Dennis D" sort="Hickstein, Dennis D" uniqKey="Hickstein D" first="Dennis D." last="Hickstein">Dennis D. Hickstein</name>
<affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="aff13">Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Horwitz, Marshall S" sort="Horwitz, Marshall S" uniqKey="Horwitz M" first="Marshall S." last="Horwitz">Marshall S. Horwitz</name>
<affiliation wicri:level="2"><nlm:aff id="aff2">Department of Pathology, University of Washington School of Medicine, Seattle, WA;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Pathology, University of Washington School of Medicine, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hahn, Christopher N" sort="Hahn, Christopher N" uniqKey="Hahn C" first="Christopher N." last="Hahn">Christopher N. Hahn</name>
<affiliation wicri:level="1"><nlm:aff id="aff8">Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff9">School of Medicine, University of Adelaide, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medicine, University of Adelaide, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Scott, Hamish S" sort="Scott, Hamish S" uniqKey="Scott H" first="Hamish S." last="Scott">Hamish S. Scott</name>
<affiliation wicri:level="1"><nlm:aff id="aff8">Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff9">School of Medicine, University of Adelaide, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medicine, University of Adelaide, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff14">School of Molecular and Biomedical Science, University of Adelaide, SA, Adelaide, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Molecular and Biomedical Science, University of Adelaide, SA, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Harvey, Natasha L" sort="Harvey, Natasha L" uniqKey="Harvey N" first="Natasha L." last="Harvey">Natasha L. Harvey</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff9">School of Medicine, University of Adelaide, Adelaide, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Medicine, University of Adelaide, Adelaide</wicri:regionArea>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Blood</title>
<idno type="ISSN">0006-4971</idno>
<idno type="eISSN">1528-0020</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Animals</term>
<term>Cells, Cultured</term>
<term>Child</term>
<term>Female</term>
<term>GATA2 Transcription Factor (genetics)</term>
<term>GATA2 Transcription Factor (metabolism)</term>
<term>GATA2 Transcription Factor (physiology)</term>
<term>Germ-Line Mutation (physiology)</term>
<term>Humans</term>
<term>Infant, Newborn</term>
<term>Leukemia, Myeloid, Acute (genetics)</term>
<term>Lymphangiogenesis (genetics)</term>
<term>Lymphatic Vessels (metabolism)</term>
<term>Lymphedema (congenital)</term>
<term>Lymphedema (genetics)</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
<term>Monocytes (pathology)</term>
<term>Myelodysplastic Syndromes (genetics)</term>
<term>Syndrome</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Animaux</term>
<term>Cellules cultivées</term>
<term>Enfant</term>
<term>Facteur de transcription GATA-2 (génétique)</term>
<term>Facteur de transcription GATA-2 (métabolisme)</term>
<term>Facteur de transcription GATA-2 (physiologie)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Leucémie aigüe myéloïde (génétique)</term>
<term>Lymphangiogenèse (génétique)</term>
<term>Lymphoedème ()</term>
<term>Lymphoedème (génétique)</term>
<term>Monocytes (anatomopathologie)</term>
<term>Mutation germinale (physiologie)</term>
<term>Mâle</term>
<term>Nouveau-né</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris transgéniques</term>
<term>Syndrome</term>
<term>Syndromes myélodysplasiques (génétique)</term>
<term>Vaisseaux lymphatiques (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>GATA2 Transcription Factor</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>GATA2 Transcription Factor</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>GATA2 Transcription Factor</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Monocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="congenital" xml:lang="en"><term>Lymphedema</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Leukemia, Myeloid, Acute</term>
<term>Lymphangiogenesis</term>
<term>Lymphedema</term>
<term>Myelodysplastic Syndromes</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur de transcription GATA-2</term>
<term>Leucémie aigüe myéloïde</term>
<term>Lymphangiogenèse</term>
<term>Lymphoedème</term>
<term>Syndromes myélodysplasiques</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lymphatic Vessels</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de transcription GATA-2</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Monocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Facteur de transcription GATA-2</term>
<term>Mutation germinale</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Germ-Line Mutation</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Animals</term>
<term>Cells, Cultured</term>
<term>Child</term>
<term>Female</term>
<term>Humans</term>
<term>Infant, Newborn</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
<term>Syndrome</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Animaux</term>
<term>Cellules cultivées</term>
<term>Enfant</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Lymphoedème</term>
<term>Mâle</term>
<term>Nouveau-né</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris transgéniques</term>
<term>Syndrome</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Recent work has established that heterozygous germline <italic>GATA2</italic>
 mutations predispose carriers to familial myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), “MonoMAC” syndrome, and DCML deficiency. Here, we describe a previously unreported MDS family carrying a missense <italic>GATA2</italic>
 mutation (p.Thr354Met), one patient with MDS/AML carrying a frameshift <italic>GATA2</italic>
 mutation (p.Leu332Thrfs*53), another with MDS harboring a <italic>GATA2</italic>
 splice site mutation, and 3 patients exhibiting MDS or MDS/AML who have large deletions encompassing the <italic>GATA2</italic>
 locus. Intriguingly, 2 MDS/AML or “MonoMAC” syndrome patients with <italic>GATA2</italic>
 deletions and one with a frameshift mutation also have primary lymphedema. Primary lymphedema occurs as a result of aberrations in the development and/or function of lymphatic vessels, spurring us to investigate whether GATA2 plays a role in the lymphatic vasculature. We demonstrate here that GATA2 protein is present at high levels in lymphatic vessel valves and that GATA2 controls the expression of genes important for programming lymphatic valve development. Our data expand the phenotypes associated with germline <italic>GATA2</italic>
 mutations to include predisposition to primary lymphedema and suggest that complete haploinsufficiency or loss of function of <italic>GATA2</italic>
, rather than missense mutations, is the key predisposing factor for lymphedema onset. Moreover, we reveal a crucial role for GATA2 in lymphatic vascular development.</p>
</div>
</front>
</TEI>
</record>

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Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature

Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature

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