Mutations in the ZNF41 Gene Are Associated with Cognitive Deficits: Identification of a New Candidate for X-Linked Mental Retardation
Identifieur interne : 000034 ( Pmc/Corpus ); précédent : 000033; suivant : 000035Mutations in the ZNF41 Gene Are Associated with Cognitive Deficits: Identification of a New Candidate for X-Linked Mental Retardation
Auteurs : Sarah A. Shoichet ; Kirsten Hoffmann ; Corinna Menzel ; Udo Trautmann ; Bettina Moser ; Maria Hoeltzenbein ; Bernard Echenne ; Michael Partington ; Hans Van Bokhoven ; Claude Moraine ; Jean-Pierre Fryns ; Jamel Chelly ; Hans-Dieter Rott ; Hans-Hilger Ropers ; Vera M. KalscheuerSource :
- American Journal of Human Genetics [ 0002-9297 ] ; 2003.
Abstract
Nonsyndromic X-linked mental retardation (MRX) is defined by an X-linked inheritance pattern of low IQ, problems with adaptive behavior, and the absence of additional specific clinical features. The 13 MRX genes identified to date account for less than one-fifth of all MRX, suggesting that numerous gene defects cause the disorder in other families. In a female patient with severe nonsyndromic mental retardation and a de novo balanced translocation t(X;7)(p11.3;q11.21), we have cloned the DNA fragment that contains the X-chromosomal and the autosomal breakpoint.
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PubMed: 14628291
PubMed Central: 1180399
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PMC:1180399Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mutations in the <italic>ZNF41</italic>
Gene Are Associated with Cognitive Deficits: Identification of a New Candidate for X-Linked Mental Retardation</title>
<author><name sortKey="Shoichet, Sarah A" sort="Shoichet, Sarah A" uniqKey="Shoichet S" first="Sarah A." last="Shoichet">Sarah A. Shoichet</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoffmann, Kirsten" sort="Hoffmann, Kirsten" uniqKey="Hoffmann K" first="Kirsten" last="Hoffmann">Kirsten Hoffmann</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Menzel, Corinna" sort="Menzel, Corinna" uniqKey="Menzel C" first="Corinna" last="Menzel">Corinna Menzel</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
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<author><name sortKey="Trautmann, Udo" sort="Trautmann, Udo" uniqKey="Trautmann U" first="Udo" last="Trautmann">Udo Trautmann</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen-Nuremberg;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moser, Bettina" sort="Moser, Bettina" uniqKey="Moser B" first="Bettina" last="Moser">Bettina Moser</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoeltzenbein, Maria" sort="Hoeltzenbein, Maria" uniqKey="Hoeltzenbein M" first="Maria" last="Hoeltzenbein">Maria Hoeltzenbein</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Echenne, Bernard" sort="Echenne, Bernard" uniqKey="Echenne B" first="Bernard" last="Echenne">Bernard Echenne</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Centre Hospitalier Universitaire de Montpellier, Hôpital Saint-Eloi, Montpellier, France,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Partington, Michael" sort="Partington, Michael" uniqKey="Partington M" first="Michael" last="Partington">Michael Partington</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Hunter Genetics and University of Newcastle, Waratah, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Van Bokhoven, Hans" sort="Van Bokhoven, Hans" uniqKey="Van Bokhoven H" first="Hans" last="Van Bokhoven">Hans Van Bokhoven</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Department of Human Genetics, University Medical Centre, Nijmegen, The Netherlands;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moraine, Claude" sort="Moraine, Claude" uniqKey="Moraine C" first="Claude" last="Moraine">Claude Moraine</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Services de Génétique–INSERM U316, CHU Bretonneau, Tours, France;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fryns, Jean Pierre" sort="Fryns, Jean Pierre" uniqKey="Fryns J" first="Jean-Pierre" last="Fryns">Jean-Pierre Fryns</name>
<affiliation><nlm:aff wicri:cut="; and" id="N0x94491a0.0x9e41228">Center for Human Genetics, Clinical Genetics Unit, Leuven, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chelly, Jamel" sort="Chelly, Jamel" uniqKey="Chelly J" first="Jamel" last="Chelly">Jamel Chelly</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Institut Cochin de Génétique Moleculaire, Centre National de la Recherche Scientifique/INSERM, CHU Cochin, Paris</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rott, Hans Dieter" sort="Rott, Hans Dieter" uniqKey="Rott H" first="Hans-Dieter" last="Rott">Hans-Dieter Rott</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen-Nuremberg;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ropers, Hans Hilger" sort="Ropers, Hans Hilger" uniqKey="Ropers H" first="Hans-Hilger" last="Ropers">Hans-Hilger Ropers</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="M Kalscheuer, Vera" sort="M Kalscheuer, Vera" uniqKey="M Kalscheuer V" first="Vera" last="M. Kalscheuer">Vera M. Kalscheuer</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Mutations in the <italic>ZNF41</italic>
Gene Are Associated with Cognitive Deficits: Identification of a New Candidate for X-Linked Mental Retardation</title>
<author><name sortKey="Shoichet, Sarah A" sort="Shoichet, Sarah A" uniqKey="Shoichet S" first="Sarah A." last="Shoichet">Sarah A. Shoichet</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoffmann, Kirsten" sort="Hoffmann, Kirsten" uniqKey="Hoffmann K" first="Kirsten" last="Hoffmann">Kirsten Hoffmann</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Menzel, Corinna" sort="Menzel, Corinna" uniqKey="Menzel C" first="Corinna" last="Menzel">Corinna Menzel</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Trautmann, Udo" sort="Trautmann, Udo" uniqKey="Trautmann U" first="Udo" last="Trautmann">Udo Trautmann</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen-Nuremberg;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moser, Bettina" sort="Moser, Bettina" uniqKey="Moser B" first="Bettina" last="Moser">Bettina Moser</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoeltzenbein, Maria" sort="Hoeltzenbein, Maria" uniqKey="Hoeltzenbein M" first="Maria" last="Hoeltzenbein">Maria Hoeltzenbein</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Echenne, Bernard" sort="Echenne, Bernard" uniqKey="Echenne B" first="Bernard" last="Echenne">Bernard Echenne</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Centre Hospitalier Universitaire de Montpellier, Hôpital Saint-Eloi, Montpellier, France,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Partington, Michael" sort="Partington, Michael" uniqKey="Partington M" first="Michael" last="Partington">Michael Partington</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Hunter Genetics and University of Newcastle, Waratah, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Van Bokhoven, Hans" sort="Van Bokhoven, Hans" uniqKey="Van Bokhoven H" first="Hans" last="Van Bokhoven">Hans Van Bokhoven</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Department of Human Genetics, University Medical Centre, Nijmegen, The Netherlands;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moraine, Claude" sort="Moraine, Claude" uniqKey="Moraine C" first="Claude" last="Moraine">Claude Moraine</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Services de Génétique–INSERM U316, CHU Bretonneau, Tours, France;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fryns, Jean Pierre" sort="Fryns, Jean Pierre" uniqKey="Fryns J" first="Jean-Pierre" last="Fryns">Jean-Pierre Fryns</name>
<affiliation><nlm:aff wicri:cut="; and" id="N0x94491a0.0x9e41228">Center for Human Genetics, Clinical Genetics Unit, Leuven, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chelly, Jamel" sort="Chelly, Jamel" uniqKey="Chelly J" first="Jamel" last="Chelly">Jamel Chelly</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Institut Cochin de Génétique Moleculaire, Centre National de la Recherche Scientifique/INSERM, CHU Cochin, Paris</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rott, Hans Dieter" sort="Rott, Hans Dieter" uniqKey="Rott H" first="Hans-Dieter" last="Rott">Hans-Dieter Rott</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen-Nuremberg;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ropers, Hans Hilger" sort="Ropers, Hans Hilger" uniqKey="Ropers H" first="Hans-Hilger" last="Ropers">Hans-Hilger Ropers</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="M Kalscheuer, Vera" sort="M Kalscheuer, Vera" uniqKey="M Kalscheuer V" first="Vera" last="M. Kalscheuer">Vera M. Kalscheuer</name>
<affiliation><nlm:aff id="N0x94491a0.0x9e41228">Max-Planck-Institute for Molecular Genetics, Berlin;</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">American Journal of Human Genetics</title>
<idno type="ISSN">0002-9297</idno>
<idno type="eISSN">1537-6605</idno>
<imprint><date when="2003">2003</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p>Nonsyndromic X-linked mental retardation (MRX) is defined by an X-linked inheritance pattern of low IQ, problems with adaptive behavior, and the absence of additional specific clinical features. The 13 MRX genes identified to date account for less than one-fifth of all MRX, suggesting that numerous gene defects cause the disorder in other families. In a female patient with severe nonsyndromic mental retardation and a de novo balanced translocation t(X;7)(p11.3;q11.21), we have cloned the DNA fragment that contains the X-chromosomal and the autosomal breakpoint. <italic>In silico</italic>
sequence analysis provided no indication of a causative role for the chromosome 7 breakpoint in mental retardation (MR), whereas, on the X chromosome, a zinc-finger gene, <italic>ZNF41,</italic>
was found to be disrupted. Expression studies indicated that <italic>ZNF41</italic>
transcripts are absent in the patient cell line, suggesting that the mental disorder in this patient results from loss of functional ZNF41. Moreover, screening of a panel of patients with MRX led to the identification of two other <italic>ZNF41</italic>
mutations that were not found in healthy control individuals. A proline-to-leucine amino acid exchange is present in affected members of one family with MRX. A second family carries an intronic splice-site mutation that results in loss of specific <italic>ZNF41</italic>
splice variants. Wild-type ZNF41 contains a highly conserved transcriptional repressor domain that is linked to mechanisms of chromatin remodeling, a process that is defective in various other forms of MR. Our results suggest that ZNF41 is critical for cognitive development; further studies aim to elucidate the specific mechanisms by which ZNF41 alterations lead to MR.</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">Am J Hum Genet</journal-id>
<journal-id journal-id-type="publisher-id">AJHG</journal-id>
<journal-title>American Journal of Human Genetics</journal-title>
<issn pub-type="ppub">0002-9297</issn>
<issn pub-type="epub">1537-6605</issn>
<publisher><publisher-name>The American Society of Human Genetics</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">14628291</article-id>
<article-id pub-id-type="pmc">1180399</article-id>
<article-id pub-id-type="publisher-id">40381</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Articles</subject>
</subj-group>
</article-categories>
<title-group><article-title>Mutations in the <italic>ZNF41</italic>
Gene Are Associated with Cognitive Deficits: Identification of a New Candidate for X-Linked Mental Retardation</article-title>
<alt-title><italic>ZNF41</italic>
Mutations Are Associated with XLMR</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Shoichet</surname>
<given-names>Sarah A.</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hoffmann</surname>
<given-names>Kirsten</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Menzel</surname>
<given-names>Corinna</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Trautmann</surname>
<given-names>Udo</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moser</surname>
<given-names>Bettina</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hoeltzenbein</surname>
<given-names>Maria</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Echenne</surname>
<given-names>Bernard</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Partington</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van Bokhoven</surname>
<given-names>Hans</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moraine</surname>
<given-names>Claude</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fryns</surname>
<given-names>Jean-Pierre</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chelly</surname>
<given-names>Jamel</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rott</surname>
<given-names>Hans-Dieter</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ropers</surname>
<given-names>Hans-Hilger</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>M. Kalscheuer</surname>
<given-names>Vera</given-names>
</name>
<xref ref-type="aff" rid="N0x94491a0.0x9e41228">1</xref>
</contrib>
</contrib-group>
<aff id="N0x94491a0.0x9e41228"><sup>1</sup>
Max-Planck-Institute for Molecular Genetics, Berlin;<sup>2</sup>
Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen-Nuremberg;<sup>3</sup>
Centre Hospitalier Universitaire de Montpellier, Hôpital Saint-Eloi, Montpellier, France,<sup>4</sup>
Hunter Genetics and University of Newcastle, Waratah, Australia;<sup>5</sup>
Department of Human Genetics, University Medical Centre, Nijmegen, The Netherlands;<sup>6</sup>
Services de Génétique–INSERM U316, CHU Bretonneau, Tours, France;<sup>7</sup>
Center for Human Genetics, Clinical Genetics Unit, Leuven, Belgium; and<sup>8</sup>
Institut Cochin de Génétique Moleculaire, Centre National de la Recherche Scientifique/INSERM, CHU Cochin, Paris</aff>
<author-notes><corresp>Address for correspondence and reprints: Dr. Vera Kalscheuer, Max-Planck-Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany. E-mail: <email>kalscheu@molgen.mpg.de</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>12</month>
<year>2003</year>
</pub-date>
<pub-date pub-type="epub"><day>18</day>
<month>11</month>
<year>2003</year>
</pub-date>
<volume>73</volume>
<issue>6</issue>
<fpage>1341</fpage>
<lpage>1354</lpage>
<history><date date-type="received"><day>22</day>
<month>7</month>
<year>2003</year>
</date>
<date date-type="accepted"><day>25</day>
<month>9</month>
<year>2003</year>
</date>
</history>
<copyright-statement>© 2003 by The American Society of Human Genetics. All rights reserved.</copyright-statement>
<copyright-year>2003</copyright-year>
<self-uri>14628291</self-uri>
<abstract><p>Nonsyndromic X-linked mental retardation (MRX) is defined by an X-linked inheritance pattern of low IQ, problems with adaptive behavior, and the absence of additional specific clinical features. The 13 MRX genes identified to date account for less than one-fifth of all MRX, suggesting that numerous gene defects cause the disorder in other families. In a female patient with severe nonsyndromic mental retardation and a de novo balanced translocation t(X;7)(p11.3;q11.21), we have cloned the DNA fragment that contains the X-chromosomal and the autosomal breakpoint. <italic>In silico</italic>
sequence analysis provided no indication of a causative role for the chromosome 7 breakpoint in mental retardation (MR), whereas, on the X chromosome, a zinc-finger gene, <italic>ZNF41,</italic>
was found to be disrupted. Expression studies indicated that <italic>ZNF41</italic>
transcripts are absent in the patient cell line, suggesting that the mental disorder in this patient results from loss of functional ZNF41. Moreover, screening of a panel of patients with MRX led to the identification of two other <italic>ZNF41</italic>
mutations that were not found in healthy control individuals. A proline-to-leucine amino acid exchange is present in affected members of one family with MRX. A second family carries an intronic splice-site mutation that results in loss of specific <italic>ZNF41</italic>
splice variants. Wild-type ZNF41 contains a highly conserved transcriptional repressor domain that is linked to mechanisms of chromatin remodeling, a process that is defective in various other forms of MR. Our results suggest that ZNF41 is critical for cognitive development; further studies aim to elucidate the specific mechanisms by which ZNF41 alterations lead to MR.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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