LymphedemaV1, Main, Exploration, bibRecord, 004935

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 : 004935 ( Main/Exploration ); précédent : 004934; suivant : 004936

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 [États-Unis] ; Conrad V. Fernandez [États-Unis] ; 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 [Australie] ; Marshall S. Horwitz [États-Unis] ; Christopher N. Hahn [Australie] ; Hamish S. Scott [Australie] ; Natasha L. Harvey [Australie]

Source :

Blood [ 0006-4971 ] ; 2012.

RBID : Pascal:12-0131180

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.
Pascal (Inist)
- Adolescent, Adulte, Animaux, Cellules cultivées, Enfant, Femelle, Humains, Jeune adulte, Lymphoedème, Mâle, Nouveau-né, Souris, Souris de lignée C57BL, Souris transgéniques, Syndrome, Syndrome myélodysplasique, Lymphoedème, Lignée germinale, Facteur transcription GATA2, Mutation, Génétique, Homme, Leucémie aiguë myéloblastique, Primaire, Lymphatique, Système lymphatique, Hématologie.
Wicri :
- topic : Génétique, Homme.

English descriptors

KwdEn :
- Acute myelogenous leukemia, Adolescent, Adult, Animals, Cells, Cultured, Child, Female, GATA2 Transcription Factor (genetics), GATA2 Transcription Factor (metabolism), GATA2 Transcription Factor (physiology), Genetics, Germ line, Germ-Line Mutation (physiology), Hematology, Human, Humans, Infant, Newborn, Leukemia, Myeloid, Acute (genetics), Lymphangiogenesis (genetics), Lymphatic, Lymphatic Vessels (metabolism), Lymphatic system, Lymphedema, Lymphedema (congenital), Lymphedema (genetics), Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Monocytes (pathology), Mutation, Myelodysplastic Syndromes (genetics), Myelodysplastic syndrome, Primary, Syndrome, Transcription factor GATA2, 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

Affiliations:

Le document en format XML

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<author><name sortKey="Scott, Hamish S" sort="Scott, Hamish S" uniqKey="Scott H" first="Hamish S." last="Scott">Hamish S. Scott</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>
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<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>School of Medicine, University of Adelaide</s1>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">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</title>
<author><name sortKey="Kazenwadel, Jan" sort="Kazenwadel, Jan" uniqKey="Kazenwadel J" first="Jan" last="Kazenwadel">Jan Kazenwadel</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Haematology, Centre for Cancer Biology, SA Pathology</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
<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"><inist:fA14 i1="01"><s1>Division of Haematology, Centre for Cancer Biology, SA Pathology</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</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"><inist:fA14 i1="02"><s1>Department of Pathology, University of Washington School of Medicine</s1>
<s2>Seattle, WA</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<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"><inist:fA14 i1="03"><s1>Signature Genomics, PerkinElmer</s1>
<s2>Spokane, WA</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
</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"><inist:fA14 i1="04"><s1>St Luke's Children's Hospital, Pediatric Genetics, and State of Idaho Genetics Program, Department of Health and Welfare</s1>
<s2>Boise, ID</s2>
<s3>USA</s3>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Idaho</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cuellar Rodriguez, Jennifer" sort="Cuellar Rodriguez, Jennifer" uniqKey="Cuellar Rodriguez J" first="Jennifer" last="Cuellar-Rodriguez">Jennifer Cuellar-Rodriguez</name>
<affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH)</s1>
<s2>Bethesda, MD</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
</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"><inist:fA14 i1="05"><s1>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH)</s1>
<s2>Bethesda, MD</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dyack, Sarah" sort="Dyack, Sarah" uniqKey="Dyack S" first="Sarah" last="Dyack">Sarah Dyack</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Pediatrics, Maritime Medical Genetics Service, IWK Health Centre and Dalhousie University</s1>
<s2>Halifax, NS</s2>
<s3>USA</s3>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Halifax, NS</wicri:noRegion>
</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 wicri:level="1"><inist:fA14 i1="07"><s1>Departments of Pediatrics and Bioethics, IWK Health Centre and Dalhousie University</s1>
<s2>Halifax, NS</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Halifax, NS</wicri:noRegion>
</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"><inist:fA14 i1="08"><s1>Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>20 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>School of Medicine, University of Adelaide</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>10 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>20 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<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"><inist:fA14 i1="08"><s1>Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>20 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<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"><inist:fA14 i1="01"><s1>Division of Haematology, Centre for Cancer Biology, SA Pathology</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<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"><inist:fA14 i1="10"><s1>Fred Hutchinson Cancer Research Center</s1>
<s2>Seattle, WA</s2>
<s3>USA</s3>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Seattle Children's Hospital</s1>
<s2>Seattle</s2>
<s3>USA</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle Children's Hospital</wicri:noRegion>
</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"><inist:fA14 i1="10"><s1>Fred Hutchinson Cancer Research Center</s1>
<s2>Seattle, WA</s2>
<s3>USA</s3>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="12"><s1>Department of Genome Sciences and Department of Medicine, University of Washington</s1>
<s2>Seattle, WA</s2>
<s3>USA</s3>
<sZ>14 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author><name sortKey="Walsh, Tom" sort="Walsh, Tom" uniqKey="Walsh T" first="Tom" last="Walsh">Tom Walsh</name>
<affiliation wicri:level="4"><inist:fA14 i1="12"><s1>Department of Genome Sciences and Department of Medicine, University of Washington</s1>
<s2>Seattle, WA</s2>
<s3>USA</s3>
<sZ>14 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</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"><inist:fA14 i1="05"><s1>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH)</s1>
<s2>Bethesda, MD</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
</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="1"><inist:fA14 i1="13"><s1>Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD; and "School of Molecular and Biomedical Science, University of Adelaide</s1>
<s2>SA, Adelaide</s2>
<s3>AUS</s3>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>SA, Adelaide</wicri:noRegion>
</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"><inist:fA14 i1="02"><s1>Department of Pathology, University of Washington School of Medicine</s1>
<s2>Seattle, WA</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
</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"><inist:fA14 i1="08"><s1>Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>20 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>School of Medicine, University of Adelaide</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>10 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>20 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<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"><inist:fA14 i1="08"><s1>Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>20 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>School of Medicine, University of Adelaide</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>10 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>20 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<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"><inist:fA14 i1="01"><s1>Division of Haematology, Centre for Cancer Biology, SA Pathology</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>School of Medicine, University of Adelaide</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>10 aut.</sZ>
<sZ>19 aut.</sZ>
<sZ>20 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Blood</title>
<title level="j" type="abbreviated">Blood</title>
<idno type="ISSN">0006-4971</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Blood</title>
<title level="j" type="abbreviated">Blood</title>
<idno type="ISSN">0006-4971</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acute myelogenous leukemia</term>
<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>Genetics</term>
<term>Germ line</term>
<term>Germ-Line Mutation (physiology)</term>
<term>Hematology</term>
<term>Human</term>
<term>Humans</term>
<term>Infant, Newborn</term>
<term>Leukemia, Myeloid, Acute (genetics)</term>
<term>Lymphangiogenesis (genetics)</term>
<term>Lymphatic</term>
<term>Lymphatic Vessels (metabolism)</term>
<term>Lymphatic system</term>
<term>Lymphedema</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>Mutation</term>
<term>Myelodysplastic Syndromes (genetics)</term>
<term>Myelodysplastic syndrome</term>
<term>Primary</term>
<term>Syndrome</term>
<term>Transcription factor GATA2</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="Pascal" 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>
<term>Syndrome myélodysplasique</term>
<term>Lymphoedème</term>
<term>Lignée germinale</term>
<term>Facteur transcription GATA2</term>
<term>Mutation</term>
<term>Génétique</term>
<term>Homme</term>
<term>Leucémie aiguë myéloblastique</term>
<term>Primaire</term>
<term>Lymphatique</term>
<term>Système lymphatique</term>
<term>Hématologie</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term>
<term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">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<sup>*</sup>
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.</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>États-Unis</li>
</country>
<region><li>Idaho</li>
<li>Maryland</li>
<li>Washington (État)</li>
</region>
<settlement><li>Seattle</li>
</settlement>
<orgName><li>Université de Washington</li>
</orgName>
</list>
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Serveur d'exploration sur le lymphœdème

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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	Serveur d'exploration sur le lymphœdème
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