A novel VEGFR3 mutation causes Milroy disease
Identifieur interne : 006955 ( Istex/Corpus ); précédent : 006954; suivant : 006956A novel VEGFR3 mutation causes Milroy disease
Auteurs : Matthew G. Butler ; Susan L. Dagenais ; Stanley G. Rockson ; Thomas W. GloverSource :
- American Journal of Medical Genetics Part A [ 1552-4825 ] ; 2007-06-01.
Abstract
Milroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with autosomal dominant inheritance. Individuals with Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor VEGFR3 (FLT‐4) are responsible for some cases with 17 mutations described to date. In this report, we describe a novel VEGFR3 mutation in exon 22 in a four‐generation family in which congenital lymphedema segregates in an autosomal dominant manner. In addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened VEGFR3 for mutations which revealed a novel 3059A > T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease. © 2007 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/ajmg.a.31703
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Glover</name><affiliation><mods:affiliation>Department of Human Genetics, University of Michigan, Ann Arbor, Michigan</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pediatrics, University of Michigan, Ann Arbor, Michigan</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">American Journal of Medical Genetics Part A</title><title level="j" type="alt">AMERICAN JOURNAL OF MEDICAL GENETICS</title><idno type="ISSN">1552-4825</idno><idno type="eISSN">1552-4833</idno><imprint><biblScope unit="vol">143A</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1212">1212</biblScope><biblScope unit="page" to="1217">1217</biblScope><biblScope unit="page-count">6</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-06-01">2007-06-01</date></imprint><idno type="ISSN">1552-4825</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1552-4825</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Milroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with autosomal dominant inheritance. Individuals with Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor VEGFR3 (FLT‐4) are responsible for some cases with 17 mutations described to date. In this report, we describe a novel VEGFR3 mutation in exon 22 in a four‐generation family in which congenital lymphedema segregates in an autosomal dominant manner. In addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened VEGFR3 for mutations which revealed a novel 3059A > T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease. © 2007 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>vegfr3</json:string><json:string>mutation</json:string><json:string>lymphedema</json:string><json:string>milroy</json:string><json:string>milroy disease</json:string><json:string>kinase</json:string><json:string>exon</json:string><json:string>karkkainen</json:string><json:string>genetics</json:string><json:string>genet</json:string><json:string>hydrocele</json:string><json:string>ghalamkarpour</json:string><json:string>allele</json:string><json:string>tyrosine kinase domains</json:string><json:string>medical genetics part</json:string><json:string>family members</json:string><json:string>second tyrosine kinase domain</json:string><json:string>vegfr3 mutations</json:string><json:string>american journal</json:string><json:string>incomplete penetrance</json:string><json:string>missense mutation</json:string><json:string>vegfr3 gene</json:string><json:string>brice</json:string><json:string>congenital</json:string><json:string>large family</json:string><json:string>primary lymphedema</json:string><json:string>tyrosine</json:string></teeft></keywords><author><json:item><name>Matthew G. Butler</name><affiliations><json:string>Department of Human Genetics, University of Michigan, Ann Arbor, Michigan</json:string><json:string>University of Michigan—Human Genetics 4909 Buhl Box 0618, 1241 E. Catherine Street, Ann Arbor, Michigan 48109‐0618.</json:string></affiliations></json:item><json:item><name>Susan L. Dagenais</name><affiliations><json:string>Department of Human Genetics, University of Michigan, Ann Arbor, Michigan</json:string></affiliations></json:item><json:item><name>Stanley G. Rockson</name><affiliations><json:string>Stanford School of Medicine, Stanford University, Stanford, California</json:string></affiliations></json:item><json:item><name>Thomas W. 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This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. 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Catherine Street, Ann Arbor, Michigan 48109‐0618.</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Susan L.</forename><surname>Dagenais</surname></persName><affiliation>Department of Human Genetics, University of Michigan, Ann Arbor, Michigan<address><country key="US"></country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">Stanley G.</forename><surname>Rockson</surname></persName><affiliation>Stanford School of Medicine, Stanford University, Stanford, California<address><country key="US"></country></address></affiliation></author><author xml:id="author-0003"><persName><forename type="first">Thomas W.</forename><surname>Glover</surname></persName><affiliation>Department of Human Genetics, University of Michigan, Ann Arbor, Michigan<address><country key="US"></country></address></affiliation><affiliation>Department of Pediatrics, University of Michigan, Ann Arbor, Michigan<address><country key="US"></country></address></affiliation></author><idno type="istex">E1195D686E1F10B2BFF5F832C699398E9AA9AA4A</idno><idno type="DOI">10.1002/ajmg.a.31703</idno><idno type="unit">AJMG31703</idno><idno type="toTypesetVersion">file:AJMG.AJMG31703.pdf</idno></analytic><monogr><title level="j" type="main">American Journal of Medical Genetics Part A</title><title level="j" type="alt">AMERICAN JOURNAL OF MEDICAL GENETICS</title><idno type="pISSN">1552-4825</idno><idno type="eISSN">1552-4833</idno><idno type="book-DOI">10.1002/(ISSN)1552-4833</idno><idno type="book-part-DOI">10.1002/ajmg.a.v143a:11</idno><idno type="product">AJMG</idno><imprint><biblScope unit="vol">143A</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1212">1212</biblScope><biblScope unit="page" to="1217">1217</biblScope><biblScope unit="page-count">6</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-06-01"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p>Milroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with autosomal dominant inheritance. Individuals with Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor <hi rend="italic">VEGFR3</hi> (<hi rend="italic">FLT‐4</hi>) are responsible for some cases with 17 mutations described to date. In this report, we describe a novel <hi rend="italic">VEGFR3</hi> mutation in exon 22 in a four‐generation family in which congenital lymphedema segregates in an autosomal dominant manner. In addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened <hi rend="italic">VEGFR3</hi> for mutations which revealed a novel 3059A > T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease. © 2007 Wiley‐Liss, Inc.</p></abstract><textClass><keywords xml:lang="en"><term xml:id="kwd1">lymphedema</term><term xml:id="kwd2">Milroy disease</term><term xml:id="kwd3">VEGFR3</term></keywords><classCode scheme="articleCategory">Clinical Report</classCode><classCode scheme="tocHeading1">Clinical Reports</classCode></textClass><langUsage><language ident="EN"></language></langUsage></profileDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/E1195D686E1F10B2BFF5F832C699398E9AA9AA4A/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1552-4833</doi><issn type="print">1552-4825</issn><issn type="electronic">1552-4833</issn><idGroup><id type="product" value="AJMG"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="AMERICAN JOURNAL OF MEDICAL GENETICS">American Journal of Medical Genetics Part A</title><title type="short">Am. 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Individuals with Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor <i>VEGFR3</i> (<i>FLT‐4</i>) are responsible for some cases with 17 mutations described to date. In this report, we describe a novel <i>VEGFR3</i> mutation in exon 22 in a four‐generation family in which congenital lymphedema segregates in an autosomal dominant manner. In addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened <i>VEGFR3</i> for mutations which revealed a novel 3059A > T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease. © 2007 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>How to cite this article: Butler MG, Dagenais SL, Rockson SG, Glover TW. 2007. A novel <i>VEGFR3</i> mutation causes Milroy disease. Am J Med Genet Part A 143A:1212–1217.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>A novel VEGFR3 mutation causes Milroy disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>NOVEL VEGFR3 MUTATION CAUSES MILROY DISEASE</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>A novel VEGFR3 mutation causes Milroy disease</title></titleInfo><name type="personal"><namePart type="given">Matthew G.</namePart><namePart type="family">Butler</namePart><affiliation>Department of Human Genetics, University of Michigan, Ann Arbor, Michigan</affiliation><affiliation>University of Michigan—Human Genetics 4909 Buhl Box 0618, 1241 E. Catherine Street, Ann Arbor, Michigan 48109‐0618.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Susan L.</namePart><namePart type="family">Dagenais</namePart><affiliation>Department of Human Genetics, University of Michigan, Ann Arbor, Michigan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stanley G.</namePart><namePart type="family">Rockson</namePart><affiliation>Stanford School of Medicine, Stanford University, Stanford, California</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas W.</namePart><namePart type="family">Glover</namePart><affiliation>Department of Human Genetics, University of Michigan, Ann Arbor, Michigan</affiliation><affiliation>Department of Pediatrics, University of Michigan, Ann Arbor, Michigan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="case-report" displayLabel="caseStudy"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2007-06-01</dateIssued><dateCaptured encoding="w3cdtf">2006-07-31</dateCaptured><dateValid encoding="w3cdtf">2007-01-01</dateValid><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">2</extent><extent unit="tables">3</extent><extent unit="references">19</extent><extent unit="words">3395</extent></physicalDescription><abstract lang="en">Milroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with autosomal dominant inheritance. Individuals with Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor VEGFR3 (FLT‐4) are responsible for some cases with 17 mutations described to date. In this report, we describe a novel VEGFR3 mutation in exon 22 in a four‐generation family in which congenital lymphedema segregates in an autosomal dominant manner. In addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened VEGFR3 for mutations which revealed a novel 3059A > T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease. © 2007 Wiley‐Liss, Inc.</abstract><note type="content">*How to cite this article: Butler MG, Dagenais SL, Rockson SG, Glover TW. 2007. A novel VEGFR3 mutation causes Milroy disease. Am J Med Genet Part A 143A:1212–1217.</note><note type="funding">National Institutes of Health - No. HL71206; </note><note type="funding">Glover from the National Heart, Lung, and Blood Institute</note><note type="funding">Michigan Predoctoral Training Program in Genetics - No. 5T32GM007544‐29; </note><subject lang="en"><genre>keywords</genre><topic>lymphedema</topic><topic>Milroy disease</topic><topic>VEGFR3</topic></subject><relatedItem type="host"><titleInfo><title>American Journal of Medical Genetics Part A</title></titleInfo><titleInfo type="abbreviated"><title>Am. J. Med. Genet.</title></titleInfo><genre type="journal">journal</genre><subject><genre>article-category</genre><topic>Clinical Report</topic></subject><identifier type="ISSN">1552-4825</identifier><identifier type="eISSN">1552-4833</identifier><identifier type="DOI">10.1002/(ISSN)1552-4833</identifier><identifier type="PublisherID">AJMG</identifier><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>143A</number></detail><detail type="issue"><caption>no.</caption><number>11</number></detail><extent unit="pages"><start>1212</start><end>1217</end><total>6</total></extent></part></relatedItem><relatedItem type="preceding"><titleInfo><title>American Journal of Medical Genetics</title></titleInfo><identifier type="ISSN">0148-7299</identifier><identifier type="ISSN">1096-8628</identifier><part><date point="end">2004</date></part></relatedItem><identifier type="istex">E1195D686E1F10B2BFF5F832C699398E9AA9AA4A</identifier><identifier type="DOI">10.1002/ajmg.a.31703</identifier><identifier type="ArticleID">AJMG31703</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2007 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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