Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Yunis-Varón Syndrome Is Caused by Mutations in <italic>FIG4</italic>, Encoding a Phosphoinositide Phosphatase</title><author><name sortKey="Campeau, Philippe M" sort="Campeau, Philippe M" uniqKey="Campeau P" first="Philippe M." last="Campeau">Philippe M. Campeau</name><affiliation><nlm:aff id="aff1">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Lenk, Guy M" sort="Lenk, Guy M" uniqKey="Lenk G" first="Guy M." last="Lenk">Guy M. Lenk</name><affiliation><nlm:aff id="aff2">Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-0618, USA</nlm:aff></affiliation></author><author><name sortKey="Lu, James T" sort="Lu, James T" uniqKey="Lu J" first="James T." last="Lu">James T. Lu</name><affiliation><nlm:aff id="aff3">Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Structural and Computational Biology & Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Bae, Yangjin" sort="Bae, Yangjin" uniqKey="Bae Y" first="Yangjin" last="Bae">Yangjin Bae</name><affiliation><nlm:aff id="aff1">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Burrage, Lindsay" sort="Burrage, Lindsay" uniqKey="Burrage L" first="Lindsay" last="Burrage">Lindsay Burrage</name><affiliation><nlm:aff id="aff1">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Turnpenny, Peter" sort="Turnpenny, Peter" uniqKey="Turnpenny P" first="Peter" last="Turnpenny">Peter Turnpenny</name><affiliation><nlm:aff id="aff5">Clinical Genetics Department, Royal Devon & Exeter Hospital, Exeter EX1 2ED, UK</nlm:aff></affiliation></author><author><name sortKey="Roman Corona Rivera, Jorge" sort="Roman Corona Rivera, Jorge" uniqKey="Roman Corona Rivera J" first="Jorge" last="Román Corona-Rivera">Jorge Román Corona-Rivera</name><affiliation><nlm:aff id="aff6">Genetics service, Division of Pediatrics, “Dr. Juan I. Menchaca” New Civil Hospital of Guadalajara, Guadalajara, Jalisco 44340, Mexico</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Institute of Human Genetics “Dr. Enrique Corona-Rivera,” Centro Universitario de Ciencias de la Salud, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico</nlm:aff></affiliation></author><author><name sortKey="Morandi, Lucia" sort="Morandi, Lucia" uniqKey="Morandi L" first="Lucia" last="Morandi">Lucia Morandi</name><affiliation><nlm:aff id="aff8">Neuromuscular Diseases and Neuroimmunology Unit, Foundation IRCCS Neurological Institute “Carlo Besta,” Milan 20133, Italy</nlm:aff></affiliation></author><author><name sortKey="Mora, Marina" sort="Mora, Marina" uniqKey="Mora M" first="Marina" last="Mora">Marina Mora</name><affiliation><nlm:aff id="aff8">Neuromuscular Diseases and Neuroimmunology Unit, Foundation IRCCS Neurological Institute “Carlo Besta,” Milan 20133, Italy</nlm:aff></affiliation></author><author><name sortKey="Reutter, Heiko" sort="Reutter, Heiko" uniqKey="Reutter H" first="Heiko" last="Reutter">Heiko Reutter</name><affiliation><nlm:aff id="aff9">Department of Neonatology and Institute of Human Genetics, Children’s Hospital, University of Bonn, Bonn 58509, Germany</nlm:aff></affiliation></author><author><name sortKey="Vulto Van Silfhout, Anneke T" sort="Vulto Van Silfhout, Anneke T" uniqKey="Vulto Van Silfhout A" first="Anneke T." last="Vulto-Van Silfhout">Anneke T. Vulto-Van Silfhout</name><affiliation><nlm:aff id="aff10">Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen 6525, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Faivre, Laurence" sort="Faivre, Laurence" uniqKey="Faivre L" first="Laurence" last="Faivre">Laurence Faivre</name><affiliation><nlm:aff id="aff11">Centre de Génétique, Centre de Référence Maladies Rares “Anomalies du Développement et Syndromes Malformatifs,” Hôpital d’Enfants, Dijon 21000, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff12">Equipe GAD EA4271, Université de Bourgogne, Dijon 21078, France</nlm:aff></affiliation></author><author><name sortKey="Haan, Eric" sort="Haan, Eric" uniqKey="Haan E" first="Eric" last="Haan">Eric Haan</name><affiliation><nlm:aff id="aff13">South Australian Clinical Genetics Service, SA Pathology at Women’s and Children’s Hospital, and Discipline of Paediatrics, The University of Adelaide, Adelaide 5006, Australia</nlm:aff></affiliation></author><author><name sortKey="Gibbs, Richard A" sort="Gibbs, Richard A" uniqKey="Gibbs R" first="Richard A." last="Gibbs">Richard A. Gibbs</name><affiliation><nlm:aff id="aff3">Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Meisler, Miriam H" sort="Meisler, Miriam H" uniqKey="Meisler M" first="Miriam H." last="Meisler">Miriam H. Meisler</name><affiliation><nlm:aff id="aff2">Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-0618, USA</nlm:aff></affiliation></author><author><name sortKey="Lee, Brendan H" sort="Lee, Brendan H" uniqKey="Lee B" first="Brendan H." last="Lee">Brendan H. Lee</name><affiliation><nlm:aff id="aff1">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff14">Howard Hughes Medical Institute, Houston, TX 77030, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23623387</idno><idno type="pmc">3644641</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644641</idno><idno type="RBID">PMC:3644641</idno><idno type="doi">10.1016/j.ajhg.2013.03.020</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">001203</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001203</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Yunis-Varón Syndrome Is Caused by Mutations in <italic>FIG4</italic>, Encoding a Phosphoinositide Phosphatase</title><author><name sortKey="Campeau, Philippe M" sort="Campeau, Philippe M" uniqKey="Campeau P" first="Philippe M." last="Campeau">Philippe M. Campeau</name><affiliation><nlm:aff id="aff1">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Lenk, Guy M" sort="Lenk, Guy M" uniqKey="Lenk G" first="Guy M." last="Lenk">Guy M. Lenk</name><affiliation><nlm:aff id="aff2">Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-0618, USA</nlm:aff></affiliation></author><author><name sortKey="Lu, James T" sort="Lu, James T" uniqKey="Lu J" first="James T." last="Lu">James T. Lu</name><affiliation><nlm:aff id="aff3">Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Structural and Computational Biology & Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Bae, Yangjin" sort="Bae, Yangjin" uniqKey="Bae Y" first="Yangjin" last="Bae">Yangjin Bae</name><affiliation><nlm:aff id="aff1">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Burrage, Lindsay" sort="Burrage, Lindsay" uniqKey="Burrage L" first="Lindsay" last="Burrage">Lindsay Burrage</name><affiliation><nlm:aff id="aff1">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Turnpenny, Peter" sort="Turnpenny, Peter" uniqKey="Turnpenny P" first="Peter" last="Turnpenny">Peter Turnpenny</name><affiliation><nlm:aff id="aff5">Clinical Genetics Department, Royal Devon & Exeter Hospital, Exeter EX1 2ED, UK</nlm:aff></affiliation></author><author><name sortKey="Roman Corona Rivera, Jorge" sort="Roman Corona Rivera, Jorge" uniqKey="Roman Corona Rivera J" first="Jorge" last="Román Corona-Rivera">Jorge Román Corona-Rivera</name><affiliation><nlm:aff id="aff6">Genetics service, Division of Pediatrics, “Dr. Juan I. Menchaca” New Civil Hospital of Guadalajara, Guadalajara, Jalisco 44340, Mexico</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Institute of Human Genetics “Dr. Enrique Corona-Rivera,” Centro Universitario de Ciencias de la Salud, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico</nlm:aff></affiliation></author><author><name sortKey="Morandi, Lucia" sort="Morandi, Lucia" uniqKey="Morandi L" first="Lucia" last="Morandi">Lucia Morandi</name><affiliation><nlm:aff id="aff8">Neuromuscular Diseases and Neuroimmunology Unit, Foundation IRCCS Neurological Institute “Carlo Besta,” Milan 20133, Italy</nlm:aff></affiliation></author><author><name sortKey="Mora, Marina" sort="Mora, Marina" uniqKey="Mora M" first="Marina" last="Mora">Marina Mora</name><affiliation><nlm:aff id="aff8">Neuromuscular Diseases and Neuroimmunology Unit, Foundation IRCCS Neurological Institute “Carlo Besta,” Milan 20133, Italy</nlm:aff></affiliation></author><author><name sortKey="Reutter, Heiko" sort="Reutter, Heiko" uniqKey="Reutter H" first="Heiko" last="Reutter">Heiko Reutter</name><affiliation><nlm:aff id="aff9">Department of Neonatology and Institute of Human Genetics, Children’s Hospital, University of Bonn, Bonn 58509, Germany</nlm:aff></affiliation></author><author><name sortKey="Vulto Van Silfhout, Anneke T" sort="Vulto Van Silfhout, Anneke T" uniqKey="Vulto Van Silfhout A" first="Anneke T." last="Vulto-Van Silfhout">Anneke T. Vulto-Van Silfhout</name><affiliation><nlm:aff id="aff10">Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen 6525, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Faivre, Laurence" sort="Faivre, Laurence" uniqKey="Faivre L" first="Laurence" last="Faivre">Laurence Faivre</name><affiliation><nlm:aff id="aff11">Centre de Génétique, Centre de Référence Maladies Rares “Anomalies du Développement et Syndromes Malformatifs,” Hôpital d’Enfants, Dijon 21000, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff12">Equipe GAD EA4271, Université de Bourgogne, Dijon 21078, France</nlm:aff></affiliation></author><author><name sortKey="Haan, Eric" sort="Haan, Eric" uniqKey="Haan E" first="Eric" last="Haan">Eric Haan</name><affiliation><nlm:aff id="aff13">South Australian Clinical Genetics Service, SA Pathology at Women’s and Children’s Hospital, and Discipline of Paediatrics, The University of Adelaide, Adelaide 5006, Australia</nlm:aff></affiliation></author><author><name sortKey="Gibbs, Richard A" sort="Gibbs, Richard A" uniqKey="Gibbs R" first="Richard A." last="Gibbs">Richard A. Gibbs</name><affiliation><nlm:aff id="aff3">Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Meisler, Miriam H" sort="Meisler, Miriam H" uniqKey="Meisler M" first="Miriam H." last="Meisler">Miriam H. Meisler</name><affiliation><nlm:aff id="aff2">Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-0618, USA</nlm:aff></affiliation></author><author><name sortKey="Lee, Brendan H" sort="Lee, Brendan H" uniqKey="Lee B" first="Brendan H." last="Lee">Brendan H. Lee</name><affiliation><nlm:aff id="aff1">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff14">Howard Hughes Medical Institute, Houston, TX 77030, USA</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="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Yunis-Varón syndrome (YVS) is an autosomal-recessive disorder with cleidocranial dysplasia, digital anomalies, and severe neurological involvement. Enlarged vacuoles are found in neurons, muscle, and cartilage. By whole-exome sequencing, we identified frameshift and missense mutations of <italic>FIG4</italic> in affected individuals from three unrelated families. <italic>FIG4</italic> encodes a phosphoinositide phosphatase required for regulation of PI(3,5)P<sub>2</sub> levels, and thus endosomal trafficking and autophagy. In a functional assay, both missense substitutions failed to correct the vacuolar phenotype of <italic>Fig4</italic>-null mouse fibroblasts. Homozygous <italic>Fig4</italic>-null mice exhibit features of YVS, including neurodegeneration and enlarged vacuoles in neurons. We demonstrate that <italic>Fig4</italic>-null mice also have small skeletons with reduced trabecular bone volume and cortical thickness and that cultured osteoblasts accumulate large vacuoles. Our findings demonstrate that homozygosity or compound heterozygosity for null mutations of <italic>FIG4</italic> is responsible for YVS, the most severe known human phenotype caused by defective phosphoinositide metabolism. In contrast, in Charcot-Marie-Tooth disease type 4J (also caused by <italic>FIG4</italic> mutations), one of the <italic>FIG4</italic> alleles is hypomorphic and disease is limited to the peripheral nervous system. This genotype-phenotype correlation demonstrates that absence of FIG4 activity leads to central nervous system dysfunction and extensive skeletal anomalies. Our results describe a role for PI(3,5)P<sub>2</sub> signaling in skeletal development and maintenance.</p></div></front></TEI><pmc article-type="brief-report"><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="iso-abbrev">Am. J. Hum. Genet</journal-id><journal-title-group><journal-title>American Journal of Human Genetics</journal-title></journal-title-group><issn pub-type="ppub">0002-9297</issn><issn pub-type="epub">1537-6605</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23623387</article-id><article-id pub-id-type="pmc">3644641</article-id><article-id pub-id-type="publisher-id">S0002-9297(13)00128-6</article-id><article-id pub-id-type="doi">10.1016/j.ajhg.2013.03.020</article-id><article-categories><subj-group subj-group-type="heading"><subject>Report</subject></subj-group></article-categories><title-group><article-title>Yunis-Varón Syndrome Is Caused by Mutations in <italic>FIG4</italic>, Encoding a Phosphoinositide Phosphatase</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Campeau</surname><given-names>Philippe M.</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="fn1" ref-type="fn">15</xref></contrib><contrib contrib-type="author"><name><surname>Lenk</surname><given-names>Guy M.</given-names></name><xref rid="aff2" ref-type="aff">2</xref><xref rid="fn1" ref-type="fn">15</xref></contrib><contrib contrib-type="author"><name><surname>Lu</surname><given-names>James T.</given-names></name><xref rid="aff3" ref-type="aff">3</xref><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Bae</surname><given-names>Yangjin</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Burrage</surname><given-names>Lindsay</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Turnpenny</surname><given-names>Peter</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Román Corona-Rivera</surname><given-names>Jorge</given-names></name><xref rid="aff6" ref-type="aff">6</xref><xref rid="aff7" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Morandi</surname><given-names>Lucia</given-names></name><xref rid="aff8" ref-type="aff">8</xref></contrib><contrib contrib-type="author"><name><surname>Mora</surname><given-names>Marina</given-names></name><xref rid="aff8" ref-type="aff">8</xref></contrib><contrib contrib-type="author"><name><surname>Reutter</surname><given-names>Heiko</given-names></name><xref rid="aff9" ref-type="aff">9</xref></contrib><contrib contrib-type="author"><name><surname>Vulto-van Silfhout</surname><given-names>Anneke T.</given-names></name><xref rid="aff10" ref-type="aff">10</xref></contrib><contrib contrib-type="author"><name><surname>Faivre</surname><given-names>Laurence</given-names></name><xref rid="aff11" ref-type="aff">11</xref><xref rid="aff12" ref-type="aff">12</xref></contrib><contrib contrib-type="author"><name><surname>Haan</surname><given-names>Eric</given-names></name><xref rid="aff13" ref-type="aff">13</xref></contrib><contrib contrib-type="author"><name><surname>Gibbs</surname><given-names>Richard A.</given-names></name><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Meisler</surname><given-names>Miriam H.</given-names></name><email>meislerm@umich.edu</email><xref rid="aff2" ref-type="aff">2</xref><xref rid="cor1" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Brendan H.</given-names></name><email>blee@bcm.edu</email><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff14" ref-type="aff">14</xref><xref rid="cor2" ref-type="corresp">**</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA</aff><aff id="aff2"><label>2</label>Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-0618, USA</aff><aff id="aff3"><label>3</label>Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA</aff><aff id="aff4"><label>4</label>Department of Structural and Computational Biology & Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030, USA</aff><aff id="aff5"><label>5</label>Clinical Genetics Department, Royal Devon & Exeter Hospital, Exeter EX1 2ED, UK</aff><aff id="aff6"><label>6</label>Genetics service, Division of Pediatrics, “Dr. Juan I. Menchaca” New Civil Hospital of Guadalajara, Guadalajara, Jalisco 44340, Mexico</aff><aff id="aff7"><label>7</label>Institute of Human Genetics “Dr. Enrique Corona-Rivera,” Centro Universitario de Ciencias de la Salud, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico</aff><aff id="aff8"><label>8</label>Neuromuscular Diseases and Neuroimmunology Unit, Foundation IRCCS Neurological Institute “Carlo Besta,” Milan 20133, Italy</aff><aff id="aff9"><label>9</label>Department of Neonatology and Institute of Human Genetics, Children’s Hospital, University of Bonn, Bonn 58509, Germany</aff><aff id="aff10"><label>10</label>Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen 6525, the Netherlands</aff><aff id="aff11"><label>11</label>Centre de Génétique, Centre de Référence Maladies Rares “Anomalies du Développement et Syndromes Malformatifs,” Hôpital d’Enfants, Dijon 21000, France</aff><aff id="aff12"><label>12</label>Equipe GAD EA4271, Université de Bourgogne, Dijon 21078, France</aff><aff id="aff13"><label>13</label>South Australian Clinical Genetics Service, SA Pathology at Women’s and Children’s Hospital, and Discipline of Paediatrics, The University of Adelaide, Adelaide 5006, Australia</aff><aff id="aff14"><label>14</label>Howard Hughes Medical Institute, Houston, TX 77030, USA</aff><author-notes><corresp id="cor1"><label>*</label>Corresponding author <email>meislerm@umich.edu</email></corresp><corresp id="cor2"><label>**</label>Corresponding author <email>blee@bcm.edu</email></corresp><fn id="fn1"><label>15</label><p>These authors contributed equally to this work</p></fn></author-notes><pub-date pub-type="ppub"><day>02</day><month>5</month><year>2013</year></pub-date><volume>92</volume><issue>5</issue><fpage>781</fpage><lpage>791</lpage><history><date date-type="received"><day>29</day><month>1</month><year>2013</year></date><date date-type="rev-recd"><day>17</day><month>3</month><year>2013</year></date><date date-type="accepted"><day>25</day><month>3</month><year>2013</year></date></history><permissions><copyright-statement>© 2013 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved.</copyright-statement><copyright-year>2013</copyright-year><copyright-holder>The American Society of Human Genetics</copyright-holder></permissions><abstract><p>Yunis-Varón syndrome (YVS) is an autosomal-recessive disorder with cleidocranial dysplasia, digital anomalies, and severe neurological involvement. Enlarged vacuoles are found in neurons, muscle, and cartilage. By whole-exome sequencing, we identified frameshift and missense mutations of <italic>FIG4</italic> in affected individuals from three unrelated families. <italic>FIG4</italic> encodes a phosphoinositide phosphatase required for regulation of PI(3,5)P<sub>2</sub> levels, and thus endosomal trafficking and autophagy. In a functional assay, both missense substitutions failed to correct the vacuolar phenotype of <italic>Fig4</italic>-null mouse fibroblasts. Homozygous <italic>Fig4</italic>-null mice exhibit features of YVS, including neurodegeneration and enlarged vacuoles in neurons. We demonstrate that <italic>Fig4</italic>-null mice also have small skeletons with reduced trabecular bone volume and cortical thickness and that cultured osteoblasts accumulate large vacuoles. Our findings demonstrate that homozygosity or compound heterozygosity for null mutations of <italic>FIG4</italic> is responsible for YVS, the most severe known human phenotype caused by defective phosphoinositide metabolism. In contrast, in Charcot-Marie-Tooth disease type 4J (also caused by <italic>FIG4</italic> mutations), one of the <italic>FIG4</italic> alleles is hypomorphic and disease is limited to the peripheral nervous system. This genotype-phenotype correlation demonstrates that absence of FIG4 activity leads to central nervous system dysfunction and extensive skeletal anomalies. Our results describe a role for PI(3,5)P<sub>2</sub> signaling in skeletal development and maintenance.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 0012030 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 0012030 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |