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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Improving Mutation Screening in Familial Hematuric Nephropathies through Next Generation Sequencing</title><author><name sortKey="Moriniere, Vincent" sort="Moriniere, Vincent" uniqKey="Moriniere V" first="Vincent" last="Morinière">Vincent Morinière</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Departments of Genetics</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Assistance Publique des Hôpitaux de Paris, Reference Center for Renal Hereditary Disease for Children and Adults (MARHEA), Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Dahan, Karin" sort="Dahan, Karin" uniqKey="Dahan K" first="Karin" last="Dahan">Karin Dahan</name><affiliation><nlm:aff id="aff6">Department of Genetics, Institute of Pathology and Genetics, Gosselies, Belgium;</nlm:aff></affiliation></author><author><name sortKey="Hilbert, Pascale" sort="Hilbert, Pascale" uniqKey="Hilbert P" first="Pascale" last="Hilbert">Pascale Hilbert</name><affiliation><nlm:aff id="aff6">Department of Genetics, Institute of Pathology and Genetics, Gosselies, Belgium;</nlm:aff></affiliation></author><author><name sortKey="Lison, Marieline" sort="Lison, Marieline" uniqKey="Lison M" first="Marieline" last="Lison">Marieline Lison</name><affiliation><nlm:aff id="aff6">Department of Genetics, Institute of Pathology and Genetics, Gosselies, Belgium;</nlm:aff></affiliation></author><author><name sortKey="Lebbah, Said" sort="Lebbah, Said" uniqKey="Lebbah S" first="Said" last="Lebbah">Said Lebbah</name><affiliation><nlm:aff id="aff5">Assistance Publique des Hôpitaux de Paris, Reference Center for Renal Hereditary Disease for Children and Adults (MARHEA), Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Topa, Alexandra" sort="Topa, Alexandra" uniqKey="Topa A" first="Alexandra" last="Topa">Alexandra Topa</name><affiliation><nlm:aff id="aff7">Department of Clinical Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Bole Feysot, Christine" sort="Bole Feysot, Christine" uniqKey="Bole Feysot C" first="Christine" last="Bole-Feysot">Christine Bole-Feysot</name><affiliation><nlm:aff id="aff8">Genomics Platform, Imagine Institute, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Pruvost, Solenn" sort="Pruvost, Solenn" uniqKey="Pruvost S" first="Solenn" last="Pruvost">Solenn Pruvost</name><affiliation><nlm:aff id="aff8">Genomics Platform, Imagine Institute, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Nitschke, Patrick" sort="Nitschke, Patrick" uniqKey="Nitschke P" first="Patrick" last="Nitschke">Patrick Nitschke</name><affiliation><nlm:aff id="aff10">Bioinformatics Platform, Paris Descartes-Sorbonne Paris Cité University, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Plaisier, Emmanuelle" sort="Plaisier, Emmanuelle" uniqKey="Plaisier E" first="Emmanuelle" last="Plaisier">Emmanuelle Plaisier</name><affiliation><nlm:aff id="aff11">Assistance Publique des Hôpitaux de Paris, Nephrology Service, Tenon Hospital, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Knebelmann, Bertrand" sort="Knebelmann, Bertrand" uniqKey="Knebelmann B" first="Bertrand" last="Knebelmann">Bertrand Knebelmann</name><affiliation><nlm:aff wicri:cut=" and" id="aff2">Nephrology Service</nlm:aff></affiliation></author><author><name sortKey="Macher, Marie Alice" sort="Macher, Marie Alice" uniqKey="Macher M" first="Marie-Alice" last="Macher">Marie-Alice Macher</name><affiliation><nlm:aff wicri:cut="; and" id="aff12">Assistance Publique des Hôpitaux de Paris, Pediatric Nephrology Service, Robert Debré Hospital, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Noel, Laure Helene" sort="Noel, Laure Helene" uniqKey="Noel L" first="Laure-Hélène" last="Noel">Laure-Hélène Noel</name><affiliation><nlm:aff wicri:cut=", and" id="aff3">Pathology</nlm:aff></affiliation></author><author><name sortKey="Gubler, Marie Claire" sort="Gubler, Marie Claire" uniqKey="Gubler M" first="Marie-Claire" last="Gubler">Marie-Claire Gubler</name><affiliation><nlm:aff id="aff13">Institut National de la Santé et de la Recherche Médicale, Inserm UMR 1163, Laboratory of Inherited Kidney Diseases, Imagine Institute, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Antignac, Corinne" sort="Antignac, Corinne" uniqKey="Antignac C" first="Corinne" last="Antignac">Corinne Antignac</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Departments of Genetics</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Assistance Publique des Hôpitaux de Paris, Reference Center for Renal Hereditary Disease for Children and Adults (MARHEA), Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff13">Institut National de la Santé et de la Recherche Médicale, Inserm UMR 1163, Laboratory of Inherited Kidney Diseases, Imagine Institute, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff9">Paris Descartes-Sorbonne Paris Cité University</nlm:aff></affiliation></author><author><name sortKey="Heidet, Laurence" sort="Heidet, Laurence" uniqKey="Heidet L" first="Laurence" last="Heidet">Laurence Heidet</name><affiliation><nlm:aff id="aff5">Assistance Publique des Hôpitaux de Paris, Reference Center for Renal Hereditary Disease for Children and Adults (MARHEA), Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Pediatric Nephrology Service, Assistance Publique des Hôpitaux de Paris, Necker‐Enfants Malades Hospital, Paris, France;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24854265</idno><idno type="pmc">4243343</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243343</idno><idno type="RBID">PMC:4243343</idno><idno type="doi">10.1681/ASN.2013080912</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000184</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Improving Mutation Screening in Familial Hematuric Nephropathies through Next Generation Sequencing</title><author><name sortKey="Moriniere, Vincent" sort="Moriniere, Vincent" uniqKey="Moriniere V" first="Vincent" last="Morinière">Vincent Morinière</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Departments of Genetics</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Assistance Publique des Hôpitaux de Paris, Reference Center for Renal Hereditary Disease for Children and Adults (MARHEA), Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Dahan, Karin" sort="Dahan, Karin" uniqKey="Dahan K" first="Karin" last="Dahan">Karin Dahan</name><affiliation><nlm:aff id="aff6">Department of Genetics, Institute of Pathology and Genetics, Gosselies, Belgium;</nlm:aff></affiliation></author><author><name sortKey="Hilbert, Pascale" sort="Hilbert, Pascale" uniqKey="Hilbert P" first="Pascale" last="Hilbert">Pascale Hilbert</name><affiliation><nlm:aff id="aff6">Department of Genetics, Institute of Pathology and Genetics, Gosselies, Belgium;</nlm:aff></affiliation></author><author><name sortKey="Lison, Marieline" sort="Lison, Marieline" uniqKey="Lison M" first="Marieline" last="Lison">Marieline Lison</name><affiliation><nlm:aff id="aff6">Department of Genetics, Institute of Pathology and Genetics, Gosselies, Belgium;</nlm:aff></affiliation></author><author><name sortKey="Lebbah, Said" sort="Lebbah, Said" uniqKey="Lebbah S" first="Said" last="Lebbah">Said Lebbah</name><affiliation><nlm:aff id="aff5">Assistance Publique des Hôpitaux de Paris, Reference Center for Renal Hereditary Disease for Children and Adults (MARHEA), Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Topa, Alexandra" sort="Topa, Alexandra" uniqKey="Topa A" first="Alexandra" last="Topa">Alexandra Topa</name><affiliation><nlm:aff id="aff7">Department of Clinical Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Bole Feysot, Christine" sort="Bole Feysot, Christine" uniqKey="Bole Feysot C" first="Christine" last="Bole-Feysot">Christine Bole-Feysot</name><affiliation><nlm:aff id="aff8">Genomics Platform, Imagine Institute, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Pruvost, Solenn" sort="Pruvost, Solenn" uniqKey="Pruvost S" first="Solenn" last="Pruvost">Solenn Pruvost</name><affiliation><nlm:aff id="aff8">Genomics Platform, Imagine Institute, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Nitschke, Patrick" sort="Nitschke, Patrick" uniqKey="Nitschke P" first="Patrick" last="Nitschke">Patrick Nitschke</name><affiliation><nlm:aff id="aff10">Bioinformatics Platform, Paris Descartes-Sorbonne Paris Cité University, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Plaisier, Emmanuelle" sort="Plaisier, Emmanuelle" uniqKey="Plaisier E" first="Emmanuelle" last="Plaisier">Emmanuelle Plaisier</name><affiliation><nlm:aff id="aff11">Assistance Publique des Hôpitaux de Paris, Nephrology Service, Tenon Hospital, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Knebelmann, Bertrand" sort="Knebelmann, Bertrand" uniqKey="Knebelmann B" first="Bertrand" last="Knebelmann">Bertrand Knebelmann</name><affiliation><nlm:aff wicri:cut=" and" id="aff2">Nephrology Service</nlm:aff></affiliation></author><author><name sortKey="Macher, Marie Alice" sort="Macher, Marie Alice" uniqKey="Macher M" first="Marie-Alice" last="Macher">Marie-Alice Macher</name><affiliation><nlm:aff wicri:cut="; and" id="aff12">Assistance Publique des Hôpitaux de Paris, Pediatric Nephrology Service, Robert Debré Hospital, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Noel, Laure Helene" sort="Noel, Laure Helene" uniqKey="Noel L" first="Laure-Hélène" last="Noel">Laure-Hélène Noel</name><affiliation><nlm:aff wicri:cut=", and" id="aff3">Pathology</nlm:aff></affiliation></author><author><name sortKey="Gubler, Marie Claire" sort="Gubler, Marie Claire" uniqKey="Gubler M" first="Marie-Claire" last="Gubler">Marie-Claire Gubler</name><affiliation><nlm:aff id="aff13">Institut National de la Santé et de la Recherche Médicale, Inserm UMR 1163, Laboratory of Inherited Kidney Diseases, Imagine Institute, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Antignac, Corinne" sort="Antignac, Corinne" uniqKey="Antignac C" first="Corinne" last="Antignac">Corinne Antignac</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Departments of Genetics</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Assistance Publique des Hôpitaux de Paris, Reference Center for Renal Hereditary Disease for Children and Adults (MARHEA), Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff13">Institut National de la Santé et de la Recherche Médicale, Inserm UMR 1163, Laboratory of Inherited Kidney Diseases, Imagine Institute, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff9">Paris Descartes-Sorbonne Paris Cité University</nlm:aff></affiliation></author><author><name sortKey="Heidet, Laurence" sort="Heidet, Laurence" uniqKey="Heidet L" first="Laurence" last="Heidet">Laurence Heidet</name><affiliation><nlm:aff id="aff5">Assistance Publique des Hôpitaux de Paris, Reference Center for Renal Hereditary Disease for Children and Adults (MARHEA), Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Pediatric Nephrology Service, Assistance Publique des Hôpitaux de Paris, Necker‐Enfants Malades Hospital, Paris, France;</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of the American Society of Nephrology : JASN</title><idno type="ISSN">1046-6673</idno><idno type="eISSN">1533-3450</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Alport syndrome is an inherited nephropathy associated with mutations in genes encoding type IV collagen chains present in the glomerular basement membrane. <italic>COL4A5</italic> mutations are associated with the major X-linked form of the disease, and <italic>COL4A3</italic> and <italic>COL4A4</italic> mutations are associated with autosomal recessive and dominant forms (thought to be involved in 15% and 1%–5% of the families, respectively) and benign familial hematuria. Mutation screening of these three large genes is time-consuming and expensive. Here, we carried out a combination of multiplex PCR, amplicon quantification, and next generation sequencing (NGS) analysis of three genes in 101 unrelated patients. We identified 88 mutations and 6 variations of unknown significance on 116 alleles in 83 patients. Two additional indel mutations were found only by secondary Sanger sequencing, but they were easily identified retrospectively with the web-based sequence visualization tool Integrative Genomics Viewer. Altogether, 75 mutations were novel. Sequencing the three genes simultaneously was particularly advantageous as the mode of inheritance could not be determined with certainty in many instances. The proportion of mutations in <italic>COL4A3</italic> and <italic>COL4A4</italic> was notably high, and the autosomal dominant forms of Alport syndrome appear more frequently than reported previously. Finally, this approach allowed the identification of large <italic>COL4A3</italic> and <italic>COL4A4</italic> rearrangements not described previously. We conclude that NGS is efficient, reduces screening time and cost, and facilitates the provision of appropriate genetic counseling in Alport syndrome.</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">J Am Soc Nephrol</journal-id><journal-id journal-id-type="iso-abbrev">J. Am. Soc. Nephrol</journal-id><journal-id journal-id-type="hwp">jnephrol</journal-id><journal-id journal-id-type="pmc">jnephrol</journal-id><journal-id journal-id-type="publisher-id">ASN</journal-id><journal-title-group><journal-title>Journal of the American Society of Nephrology : JASN</journal-title></journal-title-group><issn pub-type="ppub">1046-6673</issn><issn pub-type="epub">1533-3450</issn><publisher><publisher-name>American Society of Nephrology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24854265</article-id><article-id pub-id-type="pmc">4243343</article-id><article-id pub-id-type="publisher-id">2013080912</article-id><article-id pub-id-type="doi">10.1681/ASN.2013080912</article-id><article-categories><subj-group subj-group-type="heading"><subject>Basic Research</subject></subj-group></article-categories><title-group><article-title>Improving Mutation Screening in Familial Hematuric Nephropathies through Next Generation Sequencing</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Morinière</surname><given-names>Vincent</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="aff" rid="aff5"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dahan</surname><given-names>Karin</given-names></name><xref ref-type="aff" rid="aff6"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hilbert</surname><given-names>Pascale</given-names></name><xref ref-type="aff" rid="aff6"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lison</surname><given-names>Marieline</given-names></name><xref ref-type="aff" rid="aff6"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lebbah</surname><given-names>Said</given-names></name><xref ref-type="aff" rid="aff5"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Topa</surname><given-names>Alexandra</given-names></name><xref ref-type="aff" rid="aff7"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bole-Feysot</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="aff8"><sup>‖</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pruvost</surname><given-names>Solenn</given-names></name><xref ref-type="aff" rid="aff8"><sup>‖</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nitschke</surname><given-names>Patrick</given-names></name><xref ref-type="aff" rid="aff10"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Plaisier</surname><given-names>Emmanuelle</given-names></name><xref ref-type="aff" rid="aff11">**</xref></contrib><contrib contrib-type="author"><name><surname>Knebelmann</surname><given-names>Bertrand</given-names></name><xref ref-type="aff" rid="aff2"><sup>††</sup></xref></contrib><contrib contrib-type="author"><name><surname>Macher</surname><given-names>Marie-Alice</given-names></name><xref ref-type="aff" rid="aff12"><sup>‡‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Noel</surname><given-names>Laure-Hélène</given-names></name><xref ref-type="aff" rid="aff3"><sup>§§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gubler</surname><given-names>Marie-Claire</given-names></name><xref ref-type="aff" rid="aff13"><sup>‖‖</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Antignac</surname><given-names>Corinne</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="aff" rid="aff5"><sup>†</sup></xref><xref ref-type="aff" rid="aff13"><sup>‖‖</sup></xref><xref ref-type="aff" rid="aff9"><sup>¶¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Heidet</surname><given-names>Laurence</given-names></name><xref ref-type="aff" rid="aff5"><sup>†</sup></xref><xref ref-type="aff" rid="aff4">***</xref></contrib><aff id="aff1"><label>*</label>Departments of Genetics, and</aff><aff id="aff3"><label>§§</label>Pathology, and</aff><aff id="aff2"><label>††</label>Nephrology Service and</aff><aff id="aff4"><label>***</label>Pediatric Nephrology Service, Assistance Publique des Hôpitaux de Paris, Necker‐Enfants Malades Hospital, Paris, France;</aff><aff id="aff5"><label>†</label>Assistance Publique des Hôpitaux de Paris, Reference Center for Renal Hereditary Disease for Children and Adults (MARHEA), Paris, France;</aff><aff id="aff6"><label>‡</label>Department of Genetics, Institute of Pathology and Genetics, Gosselies, Belgium;</aff><aff id="aff7"><label>§</label>Department of Clinical Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden;</aff><aff id="aff8"><label>‖</label>Genomics Platform, Imagine Institute, Paris, France;</aff><aff id="aff9"><label>¶¶</label>Paris Descartes-Sorbonne Paris Cité University, and</aff><aff id="aff10"><label>¶</label>Bioinformatics Platform, Paris Descartes-Sorbonne Paris Cité University, Paris, France;</aff><aff id="aff11"><label>**</label>Assistance Publique des Hôpitaux de Paris, Nephrology Service, Tenon Hospital, Paris, France;</aff><aff id="aff12"><label>‡‡</label>Assistance Publique des Hôpitaux de Paris, Pediatric Nephrology Service, Robert Debré Hospital, Paris, France; and</aff><aff id="aff13"><label>‖‖</label>Institut National de la Santé et de la Recherche Médicale, Inserm UMR 1163, Laboratory of Inherited Kidney Diseases, Imagine Institute, Paris, France</aff></contrib-group><author-notes><corresp id="cor1"><bold>Correspondence:</bold> Dr. Corinne Antignac, <addr-line>APHP, Department of Genetics, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, and Inserm UMR 1163, Paris Descartes‐Sorbonne Paris Cité University, Laboratory of Hereditary Kidney Diseases, Imagine Institute, 24 Bd du Montparnasse, 75015 Paris, France</addr-line>. Email: <email>corinne.antignac@inserm.fr</email></corresp></author-notes><pub-date pub-type="ppub"><month>12</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>22</day><month>5</month><year>2014</year></pub-date><volume>25</volume><issue>12</issue><fpage>2740</fpage><lpage>2751</lpage><history><date date-type="received"><day>30</day><month>8</month><year>2013</year></date><date date-type="accepted"><day>18</day><month>3</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 by the American Society of Nephrology</copyright-statement><copyright-year>2014</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="ASN.2013080912.pdf"></self-uri><abstract><p>Alport syndrome is an inherited nephropathy associated with mutations in genes encoding type IV collagen chains present in the glomerular basement membrane. <italic>COL4A5</italic> mutations are associated with the major X-linked form of the disease, and <italic>COL4A3</italic> and <italic>COL4A4</italic> mutations are associated with autosomal recessive and dominant forms (thought to be involved in 15% and 1%–5% of the families, respectively) and benign familial hematuria. Mutation screening of these three large genes is time-consuming and expensive. Here, we carried out a combination of multiplex PCR, amplicon quantification, and next generation sequencing (NGS) analysis of three genes in 101 unrelated patients. We identified 88 mutations and 6 variations of unknown significance on 116 alleles in 83 patients. Two additional indel mutations were found only by secondary Sanger sequencing, but they were easily identified retrospectively with the web-based sequence visualization tool Integrative Genomics Viewer. Altogether, 75 mutations were novel. Sequencing the three genes simultaneously was particularly advantageous as the mode of inheritance could not be determined with certainty in many instances. The proportion of mutations in <italic>COL4A3</italic> and <italic>COL4A4</italic> was notably high, and the autosomal dominant forms of Alport syndrome appear more frequently than reported previously. Finally, this approach allowed the identification of large <italic>COL4A3</italic> and <italic>COL4A4</italic> rearrangements not described previously. We conclude that NGS is efficient, reduces screening time and cost, and facilitates the provision of appropriate genetic counseling in Alport syndrome.</p></abstract><kwd-group><kwd>Alport syndrome</kwd><kwd>genetic renal disease</kwd><kwd>molecular genetics</kwd></kwd-group><counts><page-count count="12"></page-count></counts><custom-meta-group><custom-meta><meta-name>cover-date</meta-name><meta-value>December 2014</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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