FLT4/VEGFR3 and Milroy Disease: Novel Mutations, a Review of Published Variants and Database Update
Identifieur interne : 003B54 ( Main/Exploration ); précédent : 003B53; suivant : 003B55FLT4/VEGFR3 and Milroy Disease: Novel Mutations, a Review of Published Variants and Database Update
Auteurs : Kristiana Gordon [Royaume-Uni] ; Sarah L. Spiden [Royaume-Uni] ; Fiona C. Connell [Royaume-Uni] ; Glen Brice [Royaume-Uni] ; Sally Cottrell [Royaume-Uni] ; John Short [Royaume-Uni] ; Rohan Taylor [Royaume-Uni] ; Steve Jeffery [Royaume-Uni] ; Peter S. Mortimer [Royaume-Uni] ; Sahar Mansour [Royaume-Uni] ; Pia Ostergaard [Royaume-Uni]Source :
- Human Mutation [ 1059-7794 ] ; 2013-01.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Vascular Endothelial Growth Factor Receptor-3.
- genetics : Genetic Predisposition to Disease, Lymphedema.
- Animals, Databases, Genetic, Family Health, Genetic Association Studies, Humans, Mice, Mutation.
Abstract
Milroy disease (MD) is an autosomal dominantly inherited primary lymphedema. In 1998, the gene locus for MD was mapped to 5q35.3 and variants in the VEGFR3 (FLT4) gene, encoding vascular endothelial growth factor receptor 3 (VEGFR3), were identified as being responsible for the majority of MD cases. Several reports have since been published detailing pathogenic FLT4 mutations. To date, a total of 58 different variants in FLT4, 20 of which are unpublished, have been observed in 95 families with MD. A review of published mutations is presented in this update. Furthermore, the unpublished variants are presented including clinical data. Comparison of clinical features in patients and their families with the same mutations reveals incomplete penetrance and variable expression, making genotype–phenotype correlations difficult. Most mutations are missense, but a few deletions and one splicing variant have also been reported. Several animal models have confirmed the role of VEGFR3 in lymphangiogenesis and studies show mutant VEGFR3 receptors are not phosphorylated. Here, an MD patient with the same p.Ile1053Phe change as seen in the Chy mouse is presented for the first time. This finding confirms that this mouse lineage is an excellent model for MD. All the data reviewed here has been submitted to a database based on the Leiden Open (source) Variation Database (LOVD) and is accessible online at www.lovd.nl/flt4.
Url:
DOI: 10.1002/humu.22223
Affiliations:
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Mortimer</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiac and Vascular Sciences, St George's University of London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region><settlement type="city">Londres</settlement></placeName><orgName type="university">Université de Londres</orgName></affiliation></author><author><name sortKey="Mansour, Sahar" sort="Mansour, Sahar" uniqKey="Mansour S" first="Sahar" last="Mansour">Sahar Mansour</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>SW Thames Regional Genetics Service, St. George's University of London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region><settlement type="city">Londres</settlement></placeName><orgName type="university">Université de Londres</orgName></affiliation></author><author><name sortKey="Ostergaard, Pia" sort="Ostergaard, Pia" uniqKey="Ostergaard P" first="Pia" last="Ostergaard">Pia Ostergaard</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Genetics, Biomedical Sciences, St George's University of London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region><settlement type="city">Londres</settlement></placeName><orgName type="university">Université de Londres</orgName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Royaume-Uni</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Human Mutation</title><title level="j" type="alt">HUMAN MUTATION</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><biblScope unit="vol">34</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="23">23</biblScope><biblScope unit="page" to="31">31</biblScope><biblScope unit="page-count">9</biblScope><date type="published" when="2013-01">2013-01</date></imprint><idno type="ISSN">1059-7794</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1059-7794</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Databases, Genetic</term><term>Family Health</term><term>Genetic Association Studies</term><term>Genetic Predisposition to Disease (genetics)</term><term>Humans</term><term>Lymphedema (genetics)</term><term>Mice</term><term>Mutation</term><term>Vascular Endothelial Growth Factor Receptor-3 (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Bases de données génétiques</term><term>Humains</term><term>Lymphoedème (génétique)</term><term>Mutation</term><term>Prédisposition génétique à une maladie (génétique)</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire (génétique)</term><term>Santé de la famille</term><term>Souris</term><term>Études d'associations génétiques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Vascular Endothelial Growth Factor Receptor-3</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genetic Predisposition to Disease</term><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Lymphoedème</term><term>Prédisposition génétique à une maladie</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Databases, Genetic</term><term>Family Health</term><term>Genetic Association Studies</term><term>Humans</term><term>Mice</term><term>Mutation</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Bases de données génétiques</term><term>Humains</term><term>Mutation</term><term>Santé de la famille</term><term>Souris</term><term>Études d'associations génétiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">Milroy disease (MD) is an autosomal dominantly inherited primary lymphedema. In 1998, the gene locus for MD was mapped to 5q35.3 and variants in the VEGFR3 (FLT4) gene, encoding vascular endothelial growth factor receptor 3 (VEGFR3), were identified as being responsible for the majority of MD cases. Several reports have since been published detailing pathogenic FLT4 mutations. To date, a total of 58 different variants in FLT4, 20 of which are unpublished, have been observed in 95 families with MD. A review of published mutations is presented in this update. Furthermore, the unpublished variants are presented including clinical data. Comparison of clinical features in patients and their families with the same mutations reveals incomplete penetrance and variable expression, making genotype–phenotype correlations difficult. Most mutations are missense, but a few deletions and one splicing variant have also been reported. Several animal models have confirmed the role of VEGFR3 in lymphangiogenesis and studies show mutant VEGFR3 receptors are not phosphorylated. Here, an MD patient with the same p.Ile1053Phe change as seen in the Chy mouse is presented for the first time. This finding confirms that this mouse lineage is an excellent model for MD. All the data reviewed here has been submitted to a database based on the Leiden Open (source) Variation Database (LOVD) and is accessible online at www.lovd.nl/flt4.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement><orgName><li>Université de Londres</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Gordon, Kristiana" sort="Gordon, Kristiana" uniqKey="Gordon K" first="Kristiana" last="Gordon">Kristiana Gordon</name></region><name sortKey="Brice, Glen" sort="Brice, Glen" uniqKey="Brice G" first="Glen" last="Brice">Glen Brice</name><name sortKey="Connell, Fiona C" sort="Connell, Fiona C" uniqKey="Connell F" first="Fiona C." last="Connell">Fiona C. Connell</name><name sortKey="Cottrell, Sally" sort="Cottrell, Sally" uniqKey="Cottrell S" first="Sally" last="Cottrell">Sally Cottrell</name><name sortKey="Jeffery, Steve" sort="Jeffery, Steve" uniqKey="Jeffery S" first="Steve" last="Jeffery">Steve Jeffery</name><name sortKey="Mansour, Sahar" sort="Mansour, Sahar" uniqKey="Mansour S" first="Sahar" last="Mansour">Sahar Mansour</name><name sortKey="Mortimer, Peter S" sort="Mortimer, Peter S" uniqKey="Mortimer P" first="Peter S." last="Mortimer">Peter S. Mortimer</name><name sortKey="Ostergaard, Pia" sort="Ostergaard, Pia" uniqKey="Ostergaard P" first="Pia" last="Ostergaard">Pia Ostergaard</name><name sortKey="Ostergaard, Pia" sort="Ostergaard, Pia" uniqKey="Ostergaard P" first="Pia" last="Ostergaard">Pia Ostergaard</name><name sortKey="Short, John" sort="Short, John" uniqKey="Short J" first="John" last="Short">John Short</name><name sortKey="Spiden, Sarah L" sort="Spiden, Sarah L" uniqKey="Spiden S" first="Sarah L." last="Spiden">Sarah L. Spiden</name><name sortKey="Taylor, Rohan" sort="Taylor, Rohan" uniqKey="Taylor R" first="Rohan" last="Taylor">Rohan Taylor</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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