LymphedemaV1, Pmc, Corpus, bibRecord, 002C77

GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome

Identifieur interne : 002C77 ( Pmc/Corpus ); précédent : 002C76; suivant : 002C78

GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome

Auteurs : Amy P. Hsu ; Kirby D. Johnson ; E. Liana Falcone ; Rajendran Sanalkumar ; Lauren Sanchez ; Dennis D. Hickstein ; Jennifer Cuellar-Rodriguez ; Jacob E. Lemieux ; Christa S. Zerbe ; Emery H. Bresnick ; Steven M. Holland

Source :

Blood [ 0006-4971 ] ; 2013.

RBID : PMC:3650705

Abstract

Key Points

Mutations in a conserved intronic enhancer element lead to GATA2 haploinsufficiency.

Mutations in GATA2, regardless of mutation type, lead to decreased GATA2 transcript levels and a common global transcriptional profile.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650705

DOI: 10.1182/blood-2012-08-452763
PubMed: 23502222
PubMed Central: 3650705

Links to Exploration step

PMC:3650705

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome</title>
<author><name sortKey="Hsu, Amy P" sort="Hsu, Amy P" uniqKey="Hsu A" first="Amy P." last="Hsu">Amy P. Hsu</name>
<affiliation><nlm:aff id="aff1">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Johnson, Kirby D" sort="Johnson, Kirby D" uniqKey="Johnson K" first="Kirby D." last="Johnson">Kirby D. Johnson</name>
<affiliation><nlm:aff id="aff2">Department of Cell and Regenerative Biology, University of Wisconsin–Madison Blood Research Program, Wisconsin Institutes for Medical Research, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Falcone, E Liana" sort="Falcone, E Liana" uniqKey="Falcone E" first="E. Liana" last="Falcone">E. Liana Falcone</name>
<affiliation><nlm:aff id="aff1">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sanalkumar, Rajendran" sort="Sanalkumar, Rajendran" uniqKey="Sanalkumar R" first="Rajendran" last="Sanalkumar">Rajendran Sanalkumar</name>
<affiliation><nlm:aff id="aff2">Department of Cell and Regenerative Biology, University of Wisconsin–Madison Blood Research Program, Wisconsin Institutes for Medical Research, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sanchez, Lauren" sort="Sanchez, Lauren" uniqKey="Sanchez L" first="Lauren" last="Sanchez">Lauren Sanchez</name>
<affiliation><nlm:aff id="aff3">University of California–Los Angeles School of Medicine, Los Angeles, CA;</nlm:aff>
</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><nlm:aff wicri:cut="; and" id="aff4">Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD</nlm:aff>
</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><nlm:aff id="aff1">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lemieux, Jacob E" sort="Lemieux, Jacob E" uniqKey="Lemieux J" first="Jacob E." last="Lemieux">Jacob E. Lemieux</name>
<affiliation><nlm:aff id="aff5">Harvard–Massachusetts Institute of Technology, Division of Health Sciences and Technology, Harvard Medical School, Boston, MA</nlm:aff>
</affiliation>
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<author><name sortKey="Zerbe, Christa S" sort="Zerbe, Christa S" uniqKey="Zerbe C" first="Christa S." last="Zerbe">Christa S. Zerbe</name>
<affiliation><nlm:aff id="aff1">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bresnick, Emery H" sort="Bresnick, Emery H" uniqKey="Bresnick E" first="Emery H." last="Bresnick">Emery H. Bresnick</name>
<affiliation><nlm:aff id="aff2">Department of Cell and Regenerative Biology, University of Wisconsin–Madison Blood Research Program, Wisconsin Institutes for Medical Research, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;</nlm:aff>
</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><nlm:aff id="aff1">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
</affiliation>
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<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650705</idno>
<idno type="RBID">PMC:3650705</idno>
<idno type="doi">10.1182/blood-2012-08-452763</idno>
<date when="2013">2013</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome</title>
<author><name sortKey="Hsu, Amy P" sort="Hsu, Amy P" uniqKey="Hsu A" first="Amy P." last="Hsu">Amy P. Hsu</name>
<affiliation><nlm:aff id="aff1">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Johnson, Kirby D" sort="Johnson, Kirby D" uniqKey="Johnson K" first="Kirby D." last="Johnson">Kirby D. Johnson</name>
<affiliation><nlm:aff id="aff2">Department of Cell and Regenerative Biology, University of Wisconsin–Madison Blood Research Program, Wisconsin Institutes for Medical Research, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Falcone, E Liana" sort="Falcone, E Liana" uniqKey="Falcone E" first="E. Liana" last="Falcone">E. Liana Falcone</name>
<affiliation><nlm:aff id="aff1">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sanalkumar, Rajendran" sort="Sanalkumar, Rajendran" uniqKey="Sanalkumar R" first="Rajendran" last="Sanalkumar">Rajendran Sanalkumar</name>
<affiliation><nlm:aff id="aff2">Department of Cell and Regenerative Biology, University of Wisconsin–Madison Blood Research Program, Wisconsin Institutes for Medical Research, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sanchez, Lauren" sort="Sanchez, Lauren" uniqKey="Sanchez L" first="Lauren" last="Sanchez">Lauren Sanchez</name>
<affiliation><nlm:aff id="aff3">University of California–Los Angeles School of Medicine, Los Angeles, CA;</nlm:aff>
</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><nlm:aff wicri:cut="; and" id="aff4">Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD</nlm:aff>
</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><nlm:aff id="aff1">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lemieux, Jacob E" sort="Lemieux, Jacob E" uniqKey="Lemieux J" first="Jacob E." last="Lemieux">Jacob E. Lemieux</name>
<affiliation><nlm:aff id="aff5">Harvard–Massachusetts Institute of Technology, Division of Health Sciences and Technology, Harvard Medical School, Boston, MA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zerbe, Christa S" sort="Zerbe, Christa S" uniqKey="Zerbe C" first="Christa S." last="Zerbe">Christa S. Zerbe</name>
<affiliation><nlm:aff id="aff1">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bresnick, Emery H" sort="Bresnick, Emery H" uniqKey="Bresnick E" first="Emery H." last="Bresnick">Emery H. Bresnick</name>
<affiliation><nlm:aff id="aff2">Department of Cell and Regenerative Biology, University of Wisconsin–Madison Blood Research Program, Wisconsin Institutes for Medical Research, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;</nlm:aff>
</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><nlm:aff id="aff1">Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Blood</title>
<idno type="ISSN">0006-4971</idno>
<idno type="eISSN">1528-0020</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><title>Key Points</title>
<p><list list-type="bullet"><list-item><p>Mutations in a conserved intronic enhancer element lead to <italic>GATA2</italic>
 haploinsufficiency.</p>
</list-item>
<list-item><p>Mutations in <italic>GATA2</italic>
, regardless of mutation type, lead to decreased <italic>GATA2</italic>
 transcript levels and a common global transcriptional profile.</p>
</list-item>
</list>
</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <front><journal-meta><journal-id journal-id-type="nlm-ta">Blood</journal-id>
<journal-id journal-id-type="iso-abbrev">Blood</journal-id>
<journal-id journal-id-type="hwp">bloodjournal</journal-id>
<journal-id journal-id-type="pmc">blood</journal-id>
<journal-id journal-id-type="publisher-id">Blood</journal-id>
<journal-title-group><journal-title>Blood</journal-title>
</journal-title-group>
<issn pub-type="ppub">0006-4971</issn>
<issn pub-type="epub">1528-0020</issn>
<publisher><publisher-name>American Society of Hematology</publisher-name>
<publisher-loc>Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23502222</article-id>
<article-id pub-id-type="pmc">3650705</article-id>
<article-id pub-id-type="publisher-id">2012/452763</article-id>
<article-id pub-id-type="doi">10.1182/blood-2012-08-452763</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Hematopoiesis and Stem Cells</subject>
</subj-group>
</article-categories>
<title-group><article-title>GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hsu</surname>
<given-names>Amy P.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Johnson</surname>
<given-names>Kirby D.</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Falcone</surname>
<given-names>E. Liana</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sanalkumar</surname>
<given-names>Rajendran</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sanchez</surname>
<given-names>Lauren</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hickstein</surname>
<given-names>Dennis D.</given-names>
</name>
<xref ref-type="aff" rid="aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cuellar-Rodriguez</surname>
<given-names>Jennifer</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lemieux</surname>
<given-names>Jacob E.</given-names>
</name>
<xref ref-type="aff" rid="aff5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zerbe</surname>
<given-names>Christa S.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bresnick</surname>
<given-names>Emery H.</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Holland</surname>
<given-names>Steven M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<aff id="aff1"><label>1</label>
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</aff>
<aff id="aff2"><label>2</label>
Department of Cell and Regenerative Biology, University of Wisconsin–Madison Blood Research Program, Wisconsin Institutes for Medical Research, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI;</aff>
<aff id="aff3"><label>3</label>
University of California–Los Angeles School of Medicine, Los Angeles, CA;</aff>
<aff id="aff4"><label>4</label>
Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD; and</aff>
<aff id="aff5"><label>5</label>
Harvard–Massachusetts Institute of Technology, Division of Health Sciences and Technology, Harvard Medical School, Boston, MA</aff>
</contrib-group>
<author-notes><fn fn-type="equal"><p>A.P.H. and K.D.J. contributed equally to this study.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>09</day>
<month>5</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epreprint"><day>15</day>
<month>3</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>09</day>
<month>5</month>
<year>2014</year>
</pub-date>
<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the 
 					. </pmc-comment>
      <volume>121</volume>
<issue>19</issue>
<fpage>3830</fpage>
<lpage>3837</lpage>
<history><date date-type="received"><day>27</day>
<month>8</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>09</day>
<month>3</month>
<year>2013</year>
</date>
</history>
<permissions><copyright-statement>© 2013 by The American Society of Hematology</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="3830.pdf"></self-uri>
<abstract abstract-type="executive-summary"><title>Key Points</title>
<p><list list-type="bullet"><list-item><p>Mutations in a conserved intronic enhancer element lead to <italic>GATA2</italic>
 haploinsufficiency.</p>
</list-item>
<list-item><p>Mutations in <italic>GATA2</italic>
, regardless of mutation type, lead to decreased <italic>GATA2</italic>
 transcript levels and a common global transcriptional profile.</p>
</list-item>
</list>
</p>
</abstract>
<abstract><p>Previous reports of <italic>GATA2</italic>
 mutations have focused on the coding region of the gene or full gene deletions. We recently identified 2 patients with novel insertion/deletion mutations predicted to result in mRNA nonsense-mediated decay, suggesting haploinsufficiency as the mechanism of GATA2 deficient disease. We therefore screened patients without identified exonic lesions for mutations within conserved noncoding and intronic regions. We discovered 1 patient with an intronic deletion mutation, 4 patients with point mutations within a conserved intronic element, and 3 patients with reduced or absent transcription from 1 allele. All mutations affected <italic>GATA2</italic>
 transcription. Full-length cDNA analysis provided evidence for decreased expression of the mutant alleles. The intronic deletion and point mutations considerably reduced the enhancer activity of the intron 5 enhancer. Analysis of 512 immune system genes revealed similar expression profiles in all clinically affected patients and reduced <italic>GATA2</italic>
 transcript levels. These mutations strongly support the haploinsufficient nature of GATA2 deficiency and identify transcriptional mechanisms and targets that lead to MonoMAC syndrome.</p>
</abstract>
<funding-group><award-group><funding-source id="CS100">National Institutes of Health</funding-source>
<award-id rid="CS100">DK68634</award-id>
</award-group>
</funding-group>
<counts><page-count count="8"></page-count>
</counts>
<custom-meta-group><custom-meta><meta-name>access</meta-name>
<meta-value>free</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>

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GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome

GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome

Source :

Abstract

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki