Golgi function and dysfunction in the first COG4-deficient CDG type II patient
Identifieur interne : 001319 ( Istex/Corpus ); précédent : 001318; suivant : 001320Golgi function and dysfunction in the first COG4-deficient CDG type II patient
Auteurs : Ellen Reynders ; Franois Foulquier ; Elisa Leo Teles ; Dulce Quelhas ; Willy Morelle ; Cathrine Rabouille ; Wim Annaert ; Gert MatthijsSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2009-09-01.
Abstract
The conserved oligomeric Golgi (COG) complex is a hetero-octameric complex essential for normal glycosylation and intra-Golgi transport. An increasing number of congenital disorder of glycosylation type II (CDG-II) mutations are found in COG subunits indicating its importance in glycosylation. We report a new CDG-II patient harbouring a p.R729W missense mutation in COG4 combined with a submicroscopical deletion. The resulting downregulation of COG4 expression additionally affects expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent as shown by glycerol gradient centrifugation. Moreover, our data indicate that subunits are present in a cytosolic pool and full complex formation assists tethering preceding membrane fusion. By extending this study to four other known COG-deficient patients, we now present the first comparative analysis on defects in transport, glycosylation and Golgi ultrastructure in these patients. The observed structural and biochemical abnormalities correlate with the severity of the mutation, with the COG4 mutant being the mildest. All together our results indicate that intact COG complexes are required to maintain Golgi dynamics and its associated functions. According to the current CDG nomenclature, this newly identified deficiency is designated CDG-IIj.
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DOI: 10.1093/hmg/ddp262
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France</mods:affiliation></affiliation></author><author><name sortKey="Rabouille, Cathrine" sort="Rabouille, Cathrine" uniqKey="Rabouille C" first="Cathrine" last="Rabouille">Cathrine Rabouille</name><affiliation><mods:affiliation>Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, The Cell Microscopy Center, Utrecht, The Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Annaert, Wim" sort="Annaert, Wim" uniqKey="Annaert W" first="Wim" last="Annaert">Wim Annaert</name><affiliation><mods:affiliation>Laboratory for Membrane Trafficking, Center for Human Genetics, University of Leuven and Department for Molecular and Developmental Genetics, VIB, B-3000 Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: gert.matthijs@uz.kuleuven.be</mods:affiliation></affiliation></author><author><name sortKey="Matthijs, Gert" sort="Matthijs, Gert" uniqKey="Matthijs G" first="Gert" last="Matthijs">Gert 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An increasing number of congenital disorder of glycosylation type II (CDG-II) mutations are found in COG subunits indicating its importance in glycosylation. We report a new CDG-II patient harbouring a p.R729W missense mutation in COG4 combined with a submicroscopical deletion. The resulting downregulation of COG4 expression additionally affects expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent as shown by glycerol gradient centrifugation. Moreover, our data indicate that subunits are present in a cytosolic pool and full complex formation assists tethering preceding membrane fusion. By extending this study to four other known COG-deficient patients, we now present the first comparative analysis on defects in transport, glycosylation and Golgi ultrastructure in these patients. The observed structural and biochemical abnormalities correlate with the severity of the mutation, with the COG4 mutant being the mildest. All together our results indicate that intact COG complexes are required to maintain Golgi dynamics and its associated functions. According to the current CDG nomenclature, this newly identified deficiency is designated CDG-IIj.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Ellen Reynders</name><affiliations><json:string>Laboratory for Membrane Trafficking, Center for Human Genetics, University of Leuven and Department for Molecular and Developmental Genetics, VIB, B-3000 Leuven, Belgium</json:string></affiliations></json:item><json:item><name>Franois Foulquier</name><affiliations><json:string>Laboratoire de Glycobiologie Structurale et Functionelle, USTL, Lille, France</json:string></affiliations></json:item><json:item><name>Elisa Leo Teles</name><affiliations><json:string>Department of Pediatrics, San Joo Hospital, Porto, Portugal</json:string></affiliations></json:item><json:item><name>Dulce Quelhas</name><affiliations><json:string>Institute of Medical Genetics Jacinto de Magalhes, Porto, Portugal</json:string></affiliations></json:item><json:item><name>Willy Morelle</name><affiliations><json:string>Laboratoire de Glycobiologie Structurale et Functionelle, USTL, Lille, France</json:string></affiliations></json:item><json:item><name>Cathrine Rabouille</name><affiliations><json:string>Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, The Cell Microscopy Center, Utrecht, The Netherlands</json:string></affiliations></json:item><json:item><name>Wim Annaert</name><affiliations><json:string>Laboratory for Membrane Trafficking, Center for Human Genetics, University of Leuven and Department for Molecular and Developmental Genetics, VIB, B-3000 Leuven, Belgium</json:string><json:string>E-mail: gert.matthijs@uz.kuleuven.be</json:string></affiliations></json:item><json:item><name>Gert Matthijs</name><affiliations><json:string>Laboratory for Molecular Diagnosis, Center for Human Genetics, University of Leuven, B-3000 Leuven, Belgium</json:string><json:string>E-mail: gert.matthijs@uz.kuleuven.be</json:string></affiliations></json:item></author><articleId><json:string>ddp262</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>The conserved oligomeric Golgi (COG) complex is a hetero-octameric complex essential for normal glycosylation and intra-Golgi transport. An increasing number of congenital disorder of glycosylation type II (CDG-II) mutations are found in COG subunits indicating its importance in glycosylation. We report a new CDG-II patient harbouring a p.R729W missense mutation in COG4 combined with a submicroscopical deletion. The resulting downregulation of COG4 expression additionally affects expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent as shown by glycerol gradient centrifugation. Moreover, our data indicate that subunits are present in a cytosolic pool and full complex formation assists tethering preceding membrane fusion. By extending this study to four other known COG-deficient patients, we now present the first comparative analysis on defects in transport, glycosylation and Golgi ultrastructure in these patients. The observed structural and biochemical abnormalities correlate with the severity of the mutation, with the COG4 mutant being the mildest. All together our results indicate that intact COG complexes are required to maintain Golgi dynamics and its associated functions. 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Portugal</affiliation></author><author xml:id="author-4"><persName><forename type="first">Dulce</forename><surname>Quelhas</surname></persName><affiliation>Institute of Medical Genetics Jacinto de Magalhes, Porto, Portugal</affiliation></author><author xml:id="author-5"><persName><forename type="first">Willy</forename><surname>Morelle</surname></persName><affiliation>Laboratoire de Glycobiologie Structurale et Functionelle, USTL, Lille, France</affiliation></author><author xml:id="author-6"><persName><forename type="first">Cathrine</forename><surname>Rabouille</surname></persName><affiliation>Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, The Cell Microscopy Center, Utrecht, The Netherlands</affiliation></author><author xml:id="author-7"><persName><forename type="first">Wim</forename><surname>Annaert</surname></persName><email>gert.matthijs@uz.kuleuven.be</email><note type="biography">The authors wish it to be known that, in their opinion, the first two and last two authors should be regarded as joint First/Last Authors.</note><affiliation>The authors wish it to be known that, in their opinion, the first two and last two authors should be regarded as joint First/Last Authors.</affiliation><affiliation>Laboratory for Membrane Trafficking, Center for Human Genetics, University of Leuven and Department for Molecular and Developmental Genetics, VIB, B-3000 Leuven, Belgium</affiliation></author><author xml:id="author-8"><persName><forename type="first">Gert</forename><surname>Matthijs</surname></persName><email>gert.matthijs@uz.kuleuven.be</email><note type="biography">The authors wish it to be known that, in their opinion, the first two and last two authors should be regarded as joint First/Last Authors.</note><affiliation>The authors wish it to be known that, in their opinion, the first two and last two authors should be regarded as joint First/Last Authors.</affiliation><affiliation>Laboratory for Molecular Diagnosis, 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An increasing number of congenital disorder of glycosylation type II (CDG-II) mutations are found in COG subunits indicating its importance in glycosylation. We report a new CDG-II patient harbouring a p.R729W missense mutation in COG4 combined with a submicroscopical deletion. The resulting downregulation of COG4 expression additionally affects expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent as shown by glycerol gradient centrifugation. Moreover, our data indicate that subunits are present in a cytosolic pool and full complex formation assists tethering preceding membrane fusion. By extending this study to four other known COG-deficient patients, we now present the first comparative analysis on defects in transport, glycosylation and Golgi ultrastructure in these patients. The observed structural and biochemical abnormalities correlate with the severity of the mutation, with the COG4 mutant being the mildest. All together our results indicate that intact COG complexes are required to maintain Golgi dynamics and its associated functions. According to the current CDG nomenclature, this newly identified deficiency is designated CDG-IIj.</p></abstract></profileDesc><revisionDesc><change when="2009-06-03">Created</change><change when="2009-09-01">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-10-14">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/831D37947AD7F17B4C21665F43821EEFDD165D9A/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-id journal-id-type="hwp">hmg</journal-id><journal-title>Human Molecular Genetics</journal-title><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/hmg/ddp262</article-id><article-id pub-id-type="publisher-id">ddp262</article-id><article-categories><subj-group subj-group-type="heading"><subject>ARTICLES</subject></subj-group></article-categories><title-group><article-title>Golgi function and dysfunction in the first COG4-deficient CDG type II patient</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Reynders</surname><given-names>Ellen</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="fn" rid="FN1">†</xref></contrib><contrib contrib-type="author"><name><surname>Foulquier</surname><given-names>François</given-names></name><xref ref-type="aff" rid="af2">2</xref><xref ref-type="fn" rid="FN1">†</xref></contrib><contrib contrib-type="author"><name><surname>Leão Teles</surname><given-names>Elisa</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Quelhas</surname><given-names>Dulce</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Morelle</surname><given-names>Willy</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Rabouille</surname><given-names>Cathérine</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Annaert</surname><given-names>Wim</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="corresp" rid="cor1">*</xref><xref ref-type="fn" rid="FN1">†</xref></contrib><contrib contrib-type="author"><name><surname>Matthijs</surname><given-names>Gert</given-names></name><xref ref-type="aff" rid="af6">6</xref><xref ref-type="corresp" rid="cor1">*</xref><xref ref-type="fn" rid="FN1">†</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>Laboratory for Membrane Trafficking, Center for Human Genetics</addr-line>, <institution>University of Leuven and Department for Molecular and Developmental Genetics</institution>, <addr-line>VIB, B-3000 Leuven</addr-line>, <country>Belgium</country></aff><aff id="af2"><label>2</label><addr-line>Laboratoire de Glycobiologie Structurale et Functionelle</addr-line>, <institution>USTL</institution>, <addr-line>Lille</addr-line>, <country>France</country></aff><aff id="af3"><label>3</label><addr-line>Department of Pediatrics</addr-line>, <institution>San João Hospital</institution>, <addr-line>Porto</addr-line>, <country>Portugal</country></aff><aff id="af4"><label>4</label><addr-line>Institute of Medical Genetics Jacinto de Magalhães, Porto</addr-line>, <country>Portugal</country></aff><aff id="af5"><label>5</label><addr-line>Department of Cell Biology and Institute of Biomembranes</addr-line>, <institution>University Medical Center Utrecht, The Cell Microscopy Center</institution>, <addr-line>Utrecht</addr-line>, <country>The Netherlands</country></aff><aff id="af6"><label>6</label><addr-line>Laboratory for Molecular Diagnosis, Center for Human Genetics</addr-line>, <institution>University of Leuven</institution>, <addr-line>B-3000 Leuven</addr-line>, <country>Belgium</country></aff><author-notes><fn id="FN1"><label>†</label><p>The authors wish it to be known that, in their opinion, the first two and last two authors should be regarded as joint First/Last Authors.</p></fn><corresp id="cor1"><label>*</label>To whom correspondence should be addressed at: <addr-line>Center for Human Genetics, KULeuven, Herestraat 49, B-3000 Leuven</addr-line>, <country>Belgium</country> (GM.)/<addr-line>Center for Human Genetics, KULeuven, and Department of Molecular and Developmental Genetics, VIB, Herestraat 49, B-3000 Leuven</addr-line>, <country>Belgium</country> (W.A.). Tel: <phone>+32 16346070</phone> (G.M.)/<phone>+32 16330520</phone> (W.A.); Fax: <fax>+32 16346060</fax> (G.M.)/<fax>+32 16330522</fax> (W.A.); Email: <email>gert.matthijs@uz.kuleuven.be</email> (G.M.)/<email>wim.annaert@cme.vib-kuleuven.be</email> (W.A.)</corresp></author-notes><pub-date pub-type="ppub"><day>1</day><month>9</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>3</day><month>6</month><year>2009</year></pub-date><volume>18</volume><issue>17</issue><fpage>3244</fpage><lpage>3256</lpage><history><date date-type="received"><day>27</day><month>1</month><year>2009</year></date><date date-type="accepted"><day>1</day><month>6</month><year>2009</year></date></history><copyright-statement>© 2009 The Author(s)</copyright-statement><copyright-year>2009</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/uk/"><p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</p></license><abstract><p>The conserved oligomeric Golgi (COG) complex is a hetero-octameric complex essential for normal glycosylation and intra-Golgi transport. An increasing number of congenital disorder of glycosylation type II (CDG-II) mutations are found in COG subunits indicating its importance in glycosylation. We report a new CDG-II patient harbouring a p.R729W missense mutation in COG4 combined with a submicroscopical deletion. The resulting downregulation of COG4 expression additionally affects expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent as shown by glycerol gradient centrifugation. Moreover, our data indicate that subunits are present in a cytosolic pool and full complex formation assists tethering preceding membrane fusion. By extending this study to four other known COG-deficient patients, we now present the first comparative analysis on defects in transport, glycosylation and Golgi ultrastructure in these patients. The observed structural and biochemical abnormalities correlate with the severity of the mutation, with the COG4 mutant being the mildest. All together our results indicate that intact COG complexes are required to maintain Golgi dynamics and its associated functions. According to the current CDG nomenclature, this newly identified deficiency is designated CDG-IIj.</p></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Golgi function and dysfunction in the first COG4-deficient CDG type II patient</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Golgi function and dysfunction in the first COG4-deficient CDG type II patient</title></titleInfo><name type="personal"><namePart type="given">Ellen</namePart><namePart type="family">Reynders</namePart><affiliation>Laboratory for Membrane Trafficking, Center for Human Genetics, University of Leuven and Department for Molecular and Developmental Genetics, VIB, B-3000 Leuven, Belgium</affiliation><description>The authors wish it to be known that, in their opinion, the first two and last two authors should be regarded as joint First/Last Authors.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Franois</namePart><namePart type="family">Foulquier</namePart><affiliation>Laboratoire de Glycobiologie Structurale et Functionelle, USTL, Lille, France</affiliation><description>The authors wish it to be known that, in their opinion, the first two and last two authors should be regarded as joint First/Last Authors.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elisa</namePart><namePart type="family">Leo Teles</namePart><affiliation>Department of Pediatrics, San Joo Hospital, Porto, Portugal</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dulce</namePart><namePart type="family">Quelhas</namePart><affiliation>Institute of Medical Genetics Jacinto de Magalhes, Porto, Portugal</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Willy</namePart><namePart type="family">Morelle</namePart><affiliation>Laboratoire de Glycobiologie Structurale et Functionelle, USTL, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cathrine</namePart><namePart type="family">Rabouille</namePart><affiliation>Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, The Cell Microscopy Center, Utrecht, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wim</namePart><namePart type="family">Annaert</namePart><affiliation>Laboratory for Membrane Trafficking, Center for Human Genetics, University of Leuven and Department for Molecular and Developmental Genetics, VIB, B-3000 Leuven, Belgium</affiliation><affiliation>E-mail: gert.matthijs@uz.kuleuven.be</affiliation><description>The authors wish it to be known that, in their opinion, the first two and last two authors should be regarded as joint First/Last Authors.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gert</namePart><namePart type="family">Matthijs</namePart><affiliation>Laboratory for Molecular Diagnosis, Center for Human Genetics, University of Leuven, B-3000 Leuven, Belgium</affiliation><affiliation>E-mail: gert.matthijs@uz.kuleuven.be</affiliation><description>The authors wish it to be known that, in their opinion, the first two and last two authors should be regarded as joint First/Last Authors.</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2009-09-01</dateIssued><dateCreated encoding="w3cdtf">2009-06-03</dateCreated><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>The conserved oligomeric Golgi (COG) complex is a hetero-octameric complex essential for normal glycosylation and intra-Golgi transport. An increasing number of congenital disorder of glycosylation type II (CDG-II) mutations are found in COG subunits indicating its importance in glycosylation. We report a new CDG-II patient harbouring a p.R729W missense mutation in COG4 combined with a submicroscopical deletion. The resulting downregulation of COG4 expression additionally affects expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent as shown by glycerol gradient centrifugation. Moreover, our data indicate that subunits are present in a cytosolic pool and full complex formation assists tethering preceding membrane fusion. By extending this study to four other known COG-deficient patients, we now present the first comparative analysis on defects in transport, glycosylation and Golgi ultrastructure in these patients. The observed structural and biochemical abnormalities correlate with the severity of the mutation, with the COG4 mutant being the mildest. All together our results indicate that intact COG complexes are required to maintain Golgi dynamics and its associated functions. According to the current CDG nomenclature, this newly identified deficiency is designated CDG-IIj.</abstract><note type="footnotes">The authors wish it to be known that, in their opinion, the first two and last two authors should be regarded as joint First/Last Authors.</note><relatedItem type="host"><titleInfo><title>Human Molecular Genetics</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0964-6906</identifier><identifier type="eISSN">1460-2083</identifier><identifier type="PublisherID">hmg</identifier><identifier type="PublisherID-hwp">hmg</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>18</number></detail><detail type="issue"><caption>no.</caption><number>17</number></detail><extent unit="pages"><start>3244</start><end>3256</end></extent></part></relatedItem><identifier type="istex">831D37947AD7F17B4C21665F43821EEFDD165D9A</identifier><identifier type="DOI">10.1093/hmg/ddp262</identifier><identifier type="ArticleID">ddp262</identifier><accessCondition type="use and reproduction" contentType="copyright">2009 The Author(s)</accessCondition><recordInfo><recordContentSource>OUP</recordContentSource></recordInfo></mods></metadata><covers><json:item><original>true</original><mimetype>image/tiff</mimetype><extension>tiff</extension><uri>https://api.istex.fr/document/831D37947AD7F17B4C21665F43821EEFDD165D9A/covers/tiff</uri></json:item><json:item><original>true</original><mimetype>text/html</mimetype><extension>html</extension><uri>https://api.istex.fr/document/831D37947AD7F17B4C21665F43821EEFDD165D9A/covers/html</uri></json:item></covers><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/831D37947AD7F17B4C21665F43821EEFDD165D9A/annexes/jpeg</uri></json:item><json:item><original>true</original><mimetype>image/gif</mimetype><extension>gif</extension><uri>https://api.istex.fr/document/831D37947AD7F17B4C21665F43821EEFDD165D9A/annexes/gif</uri></json:item></annexes><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/831D37947AD7F17B4C21665F43821EEFDD165D9A/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">BIOCHEMISTRY & MOLECULAR BIOLOGY</classCode><classCode scheme="WOS">GENETICS & HEREDITY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI><json:item><type>refBibs</type><uri>https://api.istex.fr/document/831D37947AD7F17B4C21665F43821EEFDD165D9A/enrichments/refBibs</uri></json:item></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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