RAD21 Mutations Cause a Human Cohesinopathy
Identifieur interne : 005968 ( Main/Exploration ); précédent : 005967; suivant : 005969RAD21 Mutations Cause a Human Cohesinopathy
Auteurs : Matthew A. Deardorff [États-Unis] ; Jonathan J. Wilde [États-Unis] ; Melanie Albrecht [Allemagne] ; Emma Dickinson [Nouvelle-Zélande] ; Stephanie Tennstedt [Allemagne] ; Diana Braunholz [Allemagne] ; Maren Mönnich [Nouvelle-Zélande] ; YUQIAN YAN [Australie] ; WEIZHEN XU [Allemagne, République populaire de Chine] ; Maria Concepcion Gil-Rodriguez [Allemagne, Espagne] ; Dinah Clark [États-Unis] ; Hakon Hakonarson [États-Unis] ; Sara Halbach [États-Unis] ; Laura Daniela Michelis [États-Unis] ; Abhinav Rampuria [États-Unis] ; Eva Rossier [Allemagne] ; Stephanie Spranger [Allemagne] ; Lionel Van Maldergem [France] ; Sally Ann Lynch [Irlande (pays)] ; Gabriele Gillessen-Kaesbach [Allemagne] ; Hermann-Josef Lüdecke [Allemagne] ; Robert G. Ramsay [Australie] ; Michael J. Mckay [Australie] ; Ian D. Krantz [États-Unis] ; HUILING XU [Australie] ; Julia A. Horsfield [Nouvelle-Zélande] ; Frank J. Kaiser [Allemagne]Source :
- American journal of human genetics [ 0002-9297 ] ; 2012.
Descripteurs français
English descriptors
Abstract
The evolutionarily conserved cohesin complex was originally described for its role in regulating sister-chromatid cohesion during mitosis and meiosis. Cohesin and its regulatory proteins have been implicated in several human developmental disorders, including Cornelia de Lange (CdLS) and Roberts syndromes. Here we show that human mutations in the integral cohesin structural protein RAD21 result in a congenital phenotype consistent with a "cohesinopathy." Children with RAD21 mutations display growth retardation, minor skeletal anomalies, and facial features that overlap findings in individuals with CdLS. Notably, unlike children with mutations in NIPBL, SMC1A, or SMC3, these individuals have much milder cognitive impairment than those with classical CdLS. Mechanistically, these mutations act at the RAD21 interface with the other cohesin proteins STAG2 and SMC1A, impair cellular DNA damage response, and disrupt transcription in a zebrafish model. Our data suggest that, compared to loss-of-function mutations, dominant missense mutations result in more severe functional defects and cause worse structural and cognitive clinical findings. These results underscore the essential role of RAD21 in eukaryotes and emphasize the need for further understanding of the role of cohesin in human development.
Affiliations:
- Allemagne, Australie, Espagne, France, Irlande (pays), Nouvelle-Zélande, République populaire de Chine, États-Unis
- Aragon, Bade-Wurtemberg, Brême (Land), District de Stuttgart, Franche-Comté, Victoria (État), Zhejiang
- Besançon, Brême, Hangzhou, Melbourne, Stuttgart
- Université de Bourgogne Franche-Comté, Université de Franche-Comté, Université de Melbourne
Links toward previous steps (curation, corpus...)
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- to stream PascalFrancis, to step Checkpoint: 000E21
- to stream Main, to step Merge: 005C56
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Le document en format XML
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Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The University of Pennsylvania Perelman School of Medicine</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>12 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>The University of Pennsylvania Perelman School of Medicine</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Center for Applied Genomics, Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA 19104</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA 19104</wicri:noRegion></affiliation></author><author><name sortKey="Halbach, Sara" sort="Halbach, Sara" uniqKey="Halbach S" first="Sara" last="Halbach">Sara Halbach</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Department of Human Genetics, University of Chicago</s1><s2>Chicago, IL 60637</s2><s3>USA</s3><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Chicago, IL 60637</wicri:noRegion></affiliation></author><author><name sortKey="Michelis, Laura Daniela" sort="Michelis, Laura Daniela" uniqKey="Michelis L" first="Laura Daniela" last="Michelis">Laura Daniela Michelis</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Genetics, The Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation></author><author><name sortKey="Rampuria, Abhinav" sort="Rampuria, Abhinav" uniqKey="Rampuria A" first="Abhinav" last="Rampuria">Abhinav Rampuria</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Genetics, The Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation></author><author><name sortKey="Rossier, Eva" sort="Rossier, Eva" uniqKey="Rossier E" first="Eva" last="Rossier">Eva Rossier</name><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Genetikum</s1><s2>Stuttgart 70174</s2><s3>DEU</s3><sZ>16 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Stuttgart</region><settlement type="city">Stuttgart</settlement></placeName></affiliation></author><author><name sortKey="Spranger, Stephanie" sort="Spranger, Stephanie" uniqKey="Spranger S" first="Stephanie" last="Spranger">Stephanie Spranger</name><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Praxis für Humangenetik</s1><s2>Bremen 28205</s2><s3>DEU</s3><sZ>17 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="3">Brême (Land)</region><settlement type="city">Brême</settlement></placeName></affiliation></author><author><name sortKey="Van Maldergem, Lionel" sort="Van Maldergem, Lionel" uniqKey="Van Maldergem L" first="Lionel" last="Van Maldergem">Lionel Van Maldergem</name><affiliation wicri:level="4"><inist:fA14 i1="13"><s1>Centre de Genetique Humaine, Universite de Franche-Comte</s1><s2>Besançon 25030</s2><s3>FRA</s3><sZ>18 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>25030</wicri:noRegion><wicri:noRegion>Universite de Franche-Comte</wicri:noRegion><placeName><settlement type="city" wicri:auto="siege">Besançon</settlement><region type="region" nuts="2">Franche-Comté</region></placeName><orgName type="university">Université de Franche-Comté</orgName><orgName type="institution" wicri:auto="newGroup">Université de Bourgogne Franche-Comté</orgName></affiliation></author><author><name sortKey="Lynch, Sally Ann" sort="Lynch, Sally Ann" uniqKey="Lynch S" first="Sally Ann" last="Lynch">Sally Ann Lynch</name><affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Our Lady's Children's Hospital, National Centre for Medical Genetics</s1><s2>Dublin 12</s2><s3>IRL</s3><sZ>19 aut.</sZ></inist:fA14><country>Irlande (pays)</country><wicri:noRegion>Dublin 12</wicri:noRegion></affiliation></author><author><name sortKey="Gillessen Kaesbach, Gabriele" sort="Gillessen Kaesbach, Gabriele" uniqKey="Gillessen Kaesbach G" first="Gabriele" last="Gillessen-Kaesbach">Gabriele Gillessen-Kaesbach</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institut fur Humangenetik Lübeck, Universität zu Lübeck</s1><s2>23538 Lübeck</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lübeck</wicri:noRegion><wicri:noRegion>Universität zu Lübeck</wicri:noRegion><wicri:noRegion>23538 Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Ludecke, Hermann Josef" sort="Ludecke, Hermann Josef" uniqKey="Ludecke H" first="Hermann-Josef" last="Lüdecke">Hermann-Josef Lüdecke</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Institut fur Humangenetik, Universitat Duisburg Essen</s1><s2>Essen 45122</s2><s3>DEU</s3><sZ>21 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>45122</wicri:noRegion><wicri:noRegion>Universitat Duisburg Essen</wicri:noRegion><wicri:noRegion>Essen 45122</wicri:noRegion></affiliation></author><author><name sortKey="Ramsay, Robert G" sort="Ramsay, Robert G" uniqKey="Ramsay R" first="Robert G." last="Ramsay">Robert G. Ramsay</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Research Division, Peter MacCallum Cancer Centre</s1><s2>East Melbourne 3002</s2><s3>AUS</s3><sZ>8 aut.</sZ><sZ>22 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>East Melbourne 3002</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="16"><s1>Sir Peter MacCallum Department of Oncology and Department of Pathology, Faculty of Medicine and Dental Sciences, The University of Melbourne, Elizabeth Street</s1><s2>Parkville, Victoria 3000</s2><s3>AUS</s3><sZ>22 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Parkville, Victoria 3000</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Mckay, Michael J" sort="Mckay, Michael J" uniqKey="Mckay M" first="Michael J." last="Mckay">Michael J. Mckay</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>North Coast Cancer Institute</s1><s2>Lismore, New South Wales 2480</s2><s3>AUS</s3><sZ>23 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>North Coast Cancer Institute</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>The University of Sydney Medical School</s1><s2>Sydney, New South Wales 2006</s2><s3>AUS</s3><sZ>23 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>The University of Sydney Medical School</wicri:noRegion></affiliation></author><author><name sortKey="Krantz, Ian D" sort="Krantz, Ian D" uniqKey="Krantz I" first="Ian D." last="Krantz">Ian D. Krantz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Genetics, The Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The University of Pennsylvania Perelman School of Medicine</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>12 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>The University of Pennsylvania Perelman School of Medicine</wicri:noRegion></affiliation></author><author><name sortKey="Huiling Xu" sort="Huiling Xu" uniqKey="Huiling Xu" last="Huiling Xu">HUILING XU</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Research Division, Peter MacCallum Cancer Centre</s1><s2>East Melbourne 3002</s2><s3>AUS</s3><sZ>8 aut.</sZ><sZ>22 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>East Melbourne 3002</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="16"><s1>Sir Peter MacCallum Department of Oncology and Department of Pathology, Faculty of Medicine and Dental Sciences, The University of Melbourne, Elizabeth Street</s1><s2>Parkville, Victoria 3000</s2><s3>AUS</s3><sZ>22 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Parkville, Victoria 3000</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Horsfield, Julia A" sort="Horsfield, Julia A" uniqKey="Horsfield J" first="Julia A." last="Horsfield">Julia A. Horsfield</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Pathology, Dunedin School of Medicine, The University of Otago</s1><s2>Dunedin 9054</s2><s3>NZL</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Nouvelle-Zélande</country><wicri:noRegion>Dunedin 9054</wicri:noRegion></affiliation></author><author><name sortKey="Kaiser, Frank J" sort="Kaiser, Frank J" uniqKey="Kaiser F" first="Frank J." last="Kaiser">Frank J. Kaiser</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institut fur Humangenetik Lübeck, Universität zu Lübeck</s1><s2>23538 Lübeck</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lübeck</wicri:noRegion><wicri:noRegion>Universität zu Lübeck</wicri:noRegion><wicri:noRegion>23538 Lübeck</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0258925</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 12-0258925 INIST</idno><idno type="RBID">Pascal:12-0258925</idno><idno type="wicri:Area/PascalFrancis/Corpus">001273</idno><idno type="wicri:Area/PascalFrancis/Curation">004C44</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000E21</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000E21</idno><idno type="wicri:doubleKey">0002-9297:2012:Deardorff M:rad:mutations:cause</idno><idno type="wicri:Area/Main/Merge">005C56</idno><idno type="wicri:Area/Main/Curation">005968</idno><idno type="wicri:Area/Main/Exploration">005968</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">RAD21 Mutations Cause a Human Cohesinopathy</title><author><name sortKey="Deardorff, Matthew A" sort="Deardorff, Matthew A" uniqKey="Deardorff M" first="Matthew A." last="Deardorff">Matthew A. Deardorff</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Genetics, The Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The University of Pennsylvania Perelman School of Medicine</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>12 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>The University of Pennsylvania Perelman School of Medicine</wicri:noRegion></affiliation></author><author><name sortKey="Wilde, Jonathan J" sort="Wilde, Jonathan J" uniqKey="Wilde J" first="Jonathan J." last="Wilde">Jonathan J. Wilde</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Genetics, The Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation></author><author><name sortKey="Albrecht, Melanie" sort="Albrecht, Melanie" uniqKey="Albrecht M" first="Melanie" last="Albrecht">Melanie Albrecht</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institut fur Humangenetik Lübeck, Universität zu Lübeck</s1><s2>23538 Lübeck</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lübeck</wicri:noRegion><wicri:noRegion>Universität zu Lübeck</wicri:noRegion><wicri:noRegion>23538 Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Dickinson, Emma" sort="Dickinson, Emma" uniqKey="Dickinson E" first="Emma" last="Dickinson">Emma Dickinson</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Pathology, Dunedin School of Medicine, The University of Otago</s1><s2>Dunedin 9054</s2><s3>NZL</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Nouvelle-Zélande</country><wicri:noRegion>Dunedin 9054</wicri:noRegion></affiliation></author><author><name sortKey="Tennstedt, Stephanie" sort="Tennstedt, Stephanie" uniqKey="Tennstedt S" first="Stephanie" last="Tennstedt">Stephanie Tennstedt</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Medizinische Klinik II, Universitat zu Liibeck</s1><s2>23538 Lubeck</s2><s3>DEU</s3><sZ>5 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lubeck</wicri:noRegion><wicri:noRegion>Universitat zu Liibeck</wicri:noRegion><wicri:noRegion>23538 Lubeck</wicri:noRegion></affiliation></author><author><name sortKey="Braunholz, Diana" sort="Braunholz, Diana" uniqKey="Braunholz D" first="Diana" last="Braunholz">Diana Braunholz</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institut fur Humangenetik Lübeck, Universität zu Lübeck</s1><s2>23538 Lübeck</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lübeck</wicri:noRegion><wicri:noRegion>Universität zu Lübeck</wicri:noRegion><wicri:noRegion>23538 Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Monnich, Maren" sort="Monnich, Maren" uniqKey="Monnich M" first="Maren" last="Mönnich">Maren Mönnich</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Pathology, Dunedin School of Medicine, The University of Otago</s1><s2>Dunedin 9054</s2><s3>NZL</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Nouvelle-Zélande</country><wicri:noRegion>Dunedin 9054</wicri:noRegion></affiliation></author><author><name sortKey="Yuqian Yan" sort="Yuqian Yan" uniqKey="Yuqian Yan" last="Yuqian Yan">YUQIAN YAN</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Research Division, Peter MacCallum Cancer Centre</s1><s2>East Melbourne 3002</s2><s3>AUS</s3><sZ>8 aut.</sZ><sZ>22 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>East Melbourne 3002</wicri:noRegion></affiliation></author><author><name sortKey="Weizhen Xu" sort="Weizhen Xu" uniqKey="Weizhen Xu" last="Weizhen Xu">WEIZHEN XU</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institut fur Humangenetik Lübeck, Universität zu Lübeck</s1><s2>23538 Lübeck</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lübeck</wicri:noRegion><wicri:noRegion>Universität zu Lübeck</wicri:noRegion><wicri:noRegion>23538 Lübeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Zhejiang Cancer Research Institute</s1><s2>Hangzhou 310058</s2><s3>CHN</s3><sZ>9 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author><author><name sortKey="Gil Rodriguez, Maria Concepcion" sort="Gil Rodriguez, Maria Concepcion" uniqKey="Gil Rodriguez M" first="Maria Concepcion" last="Gil-Rodriguez">Maria Concepcion Gil-Rodriguez</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institut fur Humangenetik Lübeck, Universität zu Lübeck</s1><s2>23538 Lübeck</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lübeck</wicri:noRegion><wicri:noRegion>Universität zu Lübeck</wicri:noRegion><wicri:noRegion>23538 Lübeck</wicri:noRegion></affiliation><affiliation wicri:level="2"><inist:fA14 i1="08"><s1>Unit of Clinical Genetics and Functional Genomics. Medical School, University of Zaragoza</s1><s2>Zaragoza 50009</s2><s3>ESP</s3><sZ>10 aut.</sZ></inist:fA14><country>Espagne</country><placeName><region nuts="2" type="communauté">Aragon</region></placeName></affiliation></author><author><name sortKey="Clark, Dinah" sort="Clark, Dinah" uniqKey="Clark D" first="Dinah" last="Clark">Dinah Clark</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Genetics, The Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation></author><author><name sortKey="Hakonarson, Hakon" sort="Hakonarson, Hakon" uniqKey="Hakonarson H" first="Hakon" last="Hakonarson">Hakon Hakonarson</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Genetics, The Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The University of Pennsylvania Perelman School of Medicine</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>12 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>The University of Pennsylvania Perelman School of Medicine</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Center for Applied Genomics, Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA 19104</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA 19104</wicri:noRegion></affiliation></author><author><name sortKey="Halbach, Sara" sort="Halbach, Sara" uniqKey="Halbach S" first="Sara" last="Halbach">Sara Halbach</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Department of Human Genetics, University of Chicago</s1><s2>Chicago, IL 60637</s2><s3>USA</s3><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Chicago, IL 60637</wicri:noRegion></affiliation></author><author><name sortKey="Michelis, Laura Daniela" sort="Michelis, Laura Daniela" uniqKey="Michelis L" first="Laura Daniela" last="Michelis">Laura Daniela Michelis</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Genetics, The Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation></author><author><name sortKey="Rampuria, Abhinav" sort="Rampuria, Abhinav" uniqKey="Rampuria A" first="Abhinav" last="Rampuria">Abhinav Rampuria</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Genetics, The Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation></author><author><name sortKey="Rossier, Eva" sort="Rossier, Eva" uniqKey="Rossier E" first="Eva" last="Rossier">Eva Rossier</name><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Genetikum</s1><s2>Stuttgart 70174</s2><s3>DEU</s3><sZ>16 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Stuttgart</region><settlement type="city">Stuttgart</settlement></placeName></affiliation></author><author><name sortKey="Spranger, Stephanie" sort="Spranger, Stephanie" uniqKey="Spranger S" first="Stephanie" last="Spranger">Stephanie Spranger</name><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Praxis für Humangenetik</s1><s2>Bremen 28205</s2><s3>DEU</s3><sZ>17 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="3">Brême (Land)</region><settlement type="city">Brême</settlement></placeName></affiliation></author><author><name sortKey="Van Maldergem, Lionel" sort="Van Maldergem, Lionel" uniqKey="Van Maldergem L" first="Lionel" last="Van Maldergem">Lionel Van Maldergem</name><affiliation wicri:level="4"><inist:fA14 i1="13"><s1>Centre de Genetique Humaine, Universite de Franche-Comte</s1><s2>Besançon 25030</s2><s3>FRA</s3><sZ>18 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>25030</wicri:noRegion><wicri:noRegion>Universite de Franche-Comte</wicri:noRegion><placeName><settlement type="city" wicri:auto="siege">Besançon</settlement><region type="region" nuts="2">Franche-Comté</region></placeName><orgName type="university">Université de Franche-Comté</orgName><orgName type="institution" wicri:auto="newGroup">Université de Bourgogne Franche-Comté</orgName></affiliation></author><author><name sortKey="Lynch, Sally Ann" sort="Lynch, Sally Ann" uniqKey="Lynch S" first="Sally Ann" last="Lynch">Sally Ann Lynch</name><affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Our Lady's Children's Hospital, National Centre for Medical Genetics</s1><s2>Dublin 12</s2><s3>IRL</s3><sZ>19 aut.</sZ></inist:fA14><country>Irlande (pays)</country><wicri:noRegion>Dublin 12</wicri:noRegion></affiliation></author><author><name sortKey="Gillessen Kaesbach, Gabriele" sort="Gillessen Kaesbach, Gabriele" uniqKey="Gillessen Kaesbach G" first="Gabriele" last="Gillessen-Kaesbach">Gabriele Gillessen-Kaesbach</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institut fur Humangenetik Lübeck, Universität zu Lübeck</s1><s2>23538 Lübeck</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lübeck</wicri:noRegion><wicri:noRegion>Universität zu Lübeck</wicri:noRegion><wicri:noRegion>23538 Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Ludecke, Hermann Josef" sort="Ludecke, Hermann Josef" uniqKey="Ludecke H" first="Hermann-Josef" last="Lüdecke">Hermann-Josef Lüdecke</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Institut fur Humangenetik, Universitat Duisburg Essen</s1><s2>Essen 45122</s2><s3>DEU</s3><sZ>21 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>45122</wicri:noRegion><wicri:noRegion>Universitat Duisburg Essen</wicri:noRegion><wicri:noRegion>Essen 45122</wicri:noRegion></affiliation></author><author><name sortKey="Ramsay, Robert G" sort="Ramsay, Robert G" uniqKey="Ramsay R" first="Robert G." last="Ramsay">Robert G. Ramsay</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Research Division, Peter MacCallum Cancer Centre</s1><s2>East Melbourne 3002</s2><s3>AUS</s3><sZ>8 aut.</sZ><sZ>22 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>East Melbourne 3002</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="16"><s1>Sir Peter MacCallum Department of Oncology and Department of Pathology, Faculty of Medicine and Dental Sciences, The University of Melbourne, Elizabeth Street</s1><s2>Parkville, Victoria 3000</s2><s3>AUS</s3><sZ>22 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Parkville, Victoria 3000</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Mckay, Michael J" sort="Mckay, Michael J" uniqKey="Mckay M" first="Michael J." last="Mckay">Michael J. Mckay</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>North Coast Cancer Institute</s1><s2>Lismore, New South Wales 2480</s2><s3>AUS</s3><sZ>23 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>North Coast Cancer Institute</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>The University of Sydney Medical School</s1><s2>Sydney, New South Wales 2006</s2><s3>AUS</s3><sZ>23 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>The University of Sydney Medical School</wicri:noRegion></affiliation></author><author><name sortKey="Krantz, Ian D" sort="Krantz, Ian D" uniqKey="Krantz I" first="Ian D." last="Krantz">Ian D. Krantz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Genetics, The Children's Hospital of Philadelphia</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, PA, 19104</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>The University of Pennsylvania Perelman School of Medicine</s1><s2>Philadelphia, PA, 19104</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>12 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>The University of Pennsylvania Perelman School of Medicine</wicri:noRegion></affiliation></author><author><name sortKey="Huiling Xu" sort="Huiling Xu" uniqKey="Huiling Xu" last="Huiling Xu">HUILING XU</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Research Division, Peter MacCallum Cancer Centre</s1><s2>East Melbourne 3002</s2><s3>AUS</s3><sZ>8 aut.</sZ><sZ>22 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>East Melbourne 3002</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="16"><s1>Sir Peter MacCallum Department of Oncology and Department of Pathology, Faculty of Medicine and Dental Sciences, The University of Melbourne, Elizabeth Street</s1><s2>Parkville, Victoria 3000</s2><s3>AUS</s3><sZ>22 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Parkville, Victoria 3000</wicri:noRegion><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Horsfield, Julia A" sort="Horsfield, Julia A" uniqKey="Horsfield J" first="Julia A." last="Horsfield">Julia A. Horsfield</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Pathology, Dunedin School of Medicine, The University of Otago</s1><s2>Dunedin 9054</s2><s3>NZL</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Nouvelle-Zélande</country><wicri:noRegion>Dunedin 9054</wicri:noRegion></affiliation></author><author><name sortKey="Kaiser, Frank J" sort="Kaiser, Frank J" uniqKey="Kaiser F" first="Frank J." last="Kaiser">Frank J. Kaiser</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institut fur Humangenetik Lübeck, Universität zu Lübeck</s1><s2>23538 Lübeck</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>20 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>23538 Lübeck</wicri:noRegion><wicri:noRegion>Universität zu Lübeck</wicri:noRegion><wicri:noRegion>23538 Lübeck</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">American journal of human genetics</title><title level="j" type="abbreviated">Am. j. hum. genet.</title><idno type="ISSN">0002-9297</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">American journal of human genetics</title><title level="j" type="abbreviated">Am. j. hum. genet.</title><idno type="ISSN">0002-9297</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Genetics</term><term>Human</term><term>Mutation</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Mutation</term><term>Homme</term><term>Génétique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term><term>Génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The evolutionarily conserved cohesin complex was originally described for its role in regulating sister-chromatid cohesion during mitosis and meiosis. Cohesin and its regulatory proteins have been implicated in several human developmental disorders, including Cornelia de Lange (CdLS) and Roberts syndromes. Here we show that human mutations in the integral cohesin structural protein RAD21 result in a congenital phenotype consistent with a "cohesinopathy." Children with RAD21 mutations display growth retardation, minor skeletal anomalies, and facial features that overlap findings in individuals with CdLS. Notably, unlike children with mutations in NIPBL, SMC1A, or SMC3, these individuals have much milder cognitive impairment than those with classical CdLS. Mechanistically, these mutations act at the RAD21 interface with the other cohesin proteins STAG2 and SMC1A, impair cellular DNA damage response, and disrupt transcription in a zebrafish model. Our data suggest that, compared to loss-of-function mutations, dominant missense mutations result in more severe functional defects and cause worse structural and cognitive clinical findings. These results underscore the essential role of RAD21 in eukaryotes and emphasize the need for further understanding of the role of cohesin in human development.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Espagne</li><li>France</li><li>Irlande (pays)</li><li>Nouvelle-Zélande</li><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Aragon</li><li>Bade-Wurtemberg</li><li>Brême (Land)</li><li>District de Stuttgart</li><li>Franche-Comté</li><li>Victoria (État)</li><li>Zhejiang</li></region><settlement><li>Besançon</li><li>Brême</li><li>Hangzhou</li><li>Melbourne</li><li>Stuttgart</li></settlement><orgName><li>Université de Bourgogne Franche-Comté</li><li>Université de Franche-Comté</li><li>Université de Melbourne</li></orgName></list><tree><country name="États-Unis"><noRegion><name sortKey="Deardorff, Matthew A" sort="Deardorff, Matthew A" uniqKey="Deardorff M" first="Matthew A." last="Deardorff">Matthew A. Deardorff</name></noRegion><name sortKey="Clark, Dinah" sort="Clark, Dinah" uniqKey="Clark D" first="Dinah" last="Clark">Dinah Clark</name><name sortKey="Deardorff, Matthew A" sort="Deardorff, Matthew A" uniqKey="Deardorff M" first="Matthew A." last="Deardorff">Matthew A. Deardorff</name><name sortKey="Hakonarson, Hakon" sort="Hakonarson, Hakon" uniqKey="Hakonarson H" first="Hakon" last="Hakonarson">Hakon Hakonarson</name><name sortKey="Hakonarson, Hakon" sort="Hakonarson, Hakon" uniqKey="Hakonarson H" first="Hakon" last="Hakonarson">Hakon Hakonarson</name><name sortKey="Hakonarson, Hakon" sort="Hakonarson, Hakon" uniqKey="Hakonarson H" first="Hakon" last="Hakonarson">Hakon Hakonarson</name><name sortKey="Halbach, Sara" sort="Halbach, Sara" uniqKey="Halbach S" first="Sara" last="Halbach">Sara Halbach</name><name sortKey="Krantz, Ian D" sort="Krantz, Ian D" uniqKey="Krantz I" first="Ian D." last="Krantz">Ian D. Krantz</name><name sortKey="Krantz, Ian D" sort="Krantz, Ian D" uniqKey="Krantz I" first="Ian D." last="Krantz">Ian D. Krantz</name><name sortKey="Michelis, Laura Daniela" sort="Michelis, Laura Daniela" uniqKey="Michelis L" first="Laura Daniela" last="Michelis">Laura Daniela Michelis</name><name sortKey="Rampuria, Abhinav" sort="Rampuria, Abhinav" uniqKey="Rampuria A" first="Abhinav" last="Rampuria">Abhinav Rampuria</name><name sortKey="Wilde, Jonathan J" sort="Wilde, Jonathan J" uniqKey="Wilde J" first="Jonathan J." last="Wilde">Jonathan J. Wilde</name></country><country name="Allemagne"><noRegion><name sortKey="Albrecht, Melanie" sort="Albrecht, Melanie" uniqKey="Albrecht M" first="Melanie" last="Albrecht">Melanie Albrecht</name></noRegion><name sortKey="Braunholz, Diana" sort="Braunholz, Diana" uniqKey="Braunholz D" first="Diana" last="Braunholz">Diana Braunholz</name><name sortKey="Gil Rodriguez, Maria Concepcion" sort="Gil Rodriguez, Maria Concepcion" uniqKey="Gil Rodriguez M" first="Maria Concepcion" last="Gil-Rodriguez">Maria Concepcion Gil-Rodriguez</name><name sortKey="Gillessen Kaesbach, Gabriele" sort="Gillessen Kaesbach, Gabriele" uniqKey="Gillessen Kaesbach G" first="Gabriele" last="Gillessen-Kaesbach">Gabriele Gillessen-Kaesbach</name><name sortKey="Kaiser, Frank J" sort="Kaiser, Frank J" uniqKey="Kaiser F" first="Frank J." last="Kaiser">Frank J. Kaiser</name><name sortKey="Ludecke, Hermann Josef" sort="Ludecke, Hermann Josef" uniqKey="Ludecke H" first="Hermann-Josef" last="Lüdecke">Hermann-Josef Lüdecke</name><name sortKey="Rossier, Eva" sort="Rossier, Eva" uniqKey="Rossier E" first="Eva" last="Rossier">Eva Rossier</name><name sortKey="Spranger, Stephanie" sort="Spranger, Stephanie" uniqKey="Spranger S" first="Stephanie" last="Spranger">Stephanie Spranger</name><name sortKey="Tennstedt, Stephanie" sort="Tennstedt, Stephanie" uniqKey="Tennstedt S" first="Stephanie" last="Tennstedt">Stephanie Tennstedt</name><name sortKey="Weizhen Xu" sort="Weizhen Xu" uniqKey="Weizhen Xu" last="Weizhen Xu">WEIZHEN XU</name></country><country name="Nouvelle-Zélande"><noRegion><name sortKey="Dickinson, Emma" sort="Dickinson, Emma" uniqKey="Dickinson E" first="Emma" last="Dickinson">Emma Dickinson</name></noRegion><name sortKey="Horsfield, Julia A" sort="Horsfield, Julia A" uniqKey="Horsfield J" first="Julia A." last="Horsfield">Julia A. Horsfield</name><name sortKey="Monnich, Maren" sort="Monnich, Maren" uniqKey="Monnich M" first="Maren" last="Mönnich">Maren Mönnich</name></country><country name="Australie"><noRegion><name sortKey="Yuqian Yan" sort="Yuqian Yan" uniqKey="Yuqian Yan" last="Yuqian Yan">YUQIAN YAN</name></noRegion><name sortKey="Huiling Xu" sort="Huiling Xu" uniqKey="Huiling Xu" last="Huiling Xu">HUILING XU</name><name sortKey="Huiling Xu" sort="Huiling Xu" uniqKey="Huiling Xu" last="Huiling Xu">HUILING XU</name><name sortKey="Mckay, Michael J" sort="Mckay, Michael J" uniqKey="Mckay M" first="Michael J." last="Mckay">Michael J. Mckay</name><name sortKey="Mckay, Michael J" sort="Mckay, Michael J" uniqKey="Mckay M" first="Michael J." last="Mckay">Michael J. Mckay</name><name sortKey="Ramsay, Robert G" sort="Ramsay, Robert G" uniqKey="Ramsay R" first="Robert G." last="Ramsay">Robert G. Ramsay</name><name sortKey="Ramsay, Robert G" sort="Ramsay, Robert G" uniqKey="Ramsay R" first="Robert G." last="Ramsay">Robert G. Ramsay</name></country><country name="République populaire de Chine"><region name="Zhejiang"><name sortKey="Weizhen Xu" sort="Weizhen Xu" uniqKey="Weizhen Xu" last="Weizhen Xu">WEIZHEN XU</name></region></country><country name="Espagne"><region name="Aragon"><name sortKey="Gil Rodriguez, Maria Concepcion" sort="Gil Rodriguez, Maria Concepcion" uniqKey="Gil Rodriguez M" first="Maria Concepcion" last="Gil-Rodriguez">Maria Concepcion Gil-Rodriguez</name></region></country><country name="France"><region name="Franche-Comté"><name sortKey="Van Maldergem, Lionel" sort="Van Maldergem, Lionel" uniqKey="Van Maldergem L" first="Lionel" last="Van Maldergem">Lionel Van Maldergem</name></region></country><country name="Irlande (pays)"><noRegion><name sortKey="Lynch, Sally Ann" sort="Lynch, Sally Ann" uniqKey="Lynch S" first="Sally Ann" last="Lynch">Sally Ann Lynch</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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