A novel missense mutation and two microrearrangements in the FOXC2 gene of three families with lymphedema-distichiasis syndrome.
Identifieur interne : 002978 ( PubMed/Checkpoint ); précédent : 002977; suivant : 002979A novel missense mutation and two microrearrangements in the FOXC2 gene of three families with lymphedema-distichiasis syndrome.
Auteurs : A-L Fauret [France] ; E. Tuleja ; X. Jeunemaitre ; S. VignesSource :
- Lymphology [ 0024-7766 ] ; 2010.
Descripteurs français
- KwdFr :
- MESH :
- génétique : Facteurs de transcription Forkhead, Lymphoedème.
- malformations : Cils.
- Adulte, Adulte d'âge moyen, Enfant, Femelle, Humains, Mutation faux-sens, Mâle, Réarrangement des gènes, Syndrome.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Forkhead Transcription Factors.
- abnormalities : Eyelashes.
- genetics : Lymphedema.
- Adult, Child, Female, Gene Rearrangement, Humans, Male, Middle Aged, Mutation, Missense, Syndrome.
Abstract
Lymphedema-distichiasis (LD) syndrome is a rare autosomal dominant disorder of the FOXC2 gene, which codes for a forkhead transcription factor. Most of the mutations described in this gene to date are deletions or insertions, suggesting a mechanism of haploinsufficiency. We studied three independent families with LD presenting with both lymphedema and distichiasis. Two microrearrangements (one 8-bp deletion and one 7-bp duplication) occurring in a GC-rich genomic region (c.893-930) known to be prone to mutations were identified. A new missense mutation (p.Lys132Glu) located in a highly conserved sequence, the forkhead domain, was also identified. Mutations in this domain have been previously shown to impair FOXC2 transactivation ability. At a genetic level, this study confirms the heterogeneity of mutations responsible for LD and is consistent with a mechanism of haploinsufficiency. At a clinical level, it reinforces the importance of genetic testing in subjects with familial lymphedema or distichiasis, since measures can be taken at an early stage to prevent complications and to reduce the progression of lymphedema or delay its occurrence.
PubMed: 20552815
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:20552815Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A novel missense mutation and two microrearrangements in the FOXC2 gene of three families with lymphedema-distichiasis syndrome.</title><author><name sortKey="Fauret, A L" sort="Fauret, A L" uniqKey="Fauret A" first="A-L" last="Fauret">A-L Fauret</name><affiliation wicri:level="1"><nlm:affiliation>Département de Génétique et Centre de Référence des Maladies Vasculaires Rares, AP-HP, Hôpital Européen Georges Pompidou Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Génétique et Centre de Référence des Maladies Vasculaires Rares, AP-HP, Hôpital Européen Georges Pompidou Paris</wicri:regionArea><wicri:noRegion>Hôpital Européen Georges Pompidou Paris</wicri:noRegion><wicri:noRegion>Hôpital Européen Georges Pompidou Paris</wicri:noRegion></affiliation></author><author><name sortKey="Tuleja, E" sort="Tuleja, E" uniqKey="Tuleja E" first="E" last="Tuleja">E. Tuleja</name></author><author><name sortKey="Jeunemaitre, X" sort="Jeunemaitre, X" uniqKey="Jeunemaitre X" first="X" last="Jeunemaitre">X. Jeunemaitre</name></author><author><name sortKey="Vignes, S" sort="Vignes, S" uniqKey="Vignes S" first="S" last="Vignes">S. Vignes</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2010">2010</date><idno type="RBID">pubmed:20552815</idno><idno type="pmid">20552815</idno><idno type="wicri:Area/PubMed/Corpus">002A35</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002A35</idno><idno type="wicri:Area/PubMed/Curation">002A35</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002A35</idno><idno type="wicri:Area/PubMed/Checkpoint">002A35</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002A35</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A novel missense mutation and two microrearrangements in the FOXC2 gene of three families with lymphedema-distichiasis syndrome.</title><author><name sortKey="Fauret, A L" sort="Fauret, A L" uniqKey="Fauret A" first="A-L" last="Fauret">A-L Fauret</name><affiliation wicri:level="1"><nlm:affiliation>Département de Génétique et Centre de Référence des Maladies Vasculaires Rares, AP-HP, Hôpital Européen Georges Pompidou Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Génétique et Centre de Référence des Maladies Vasculaires Rares, AP-HP, Hôpital Européen Georges Pompidou Paris</wicri:regionArea><wicri:noRegion>Hôpital Européen Georges Pompidou Paris</wicri:noRegion><wicri:noRegion>Hôpital Européen Georges Pompidou Paris</wicri:noRegion></affiliation></author><author><name sortKey="Tuleja, E" sort="Tuleja, E" uniqKey="Tuleja E" first="E" last="Tuleja">E. Tuleja</name></author><author><name sortKey="Jeunemaitre, X" sort="Jeunemaitre, X" uniqKey="Jeunemaitre X" first="X" last="Jeunemaitre">X. Jeunemaitre</name></author><author><name sortKey="Vignes, S" sort="Vignes, S" uniqKey="Vignes S" first="S" last="Vignes">S. Vignes</name></author></analytic><series><title level="j">Lymphology</title><idno type="ISSN">0024-7766</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Child</term><term>Eyelashes (abnormalities)</term><term>Female</term><term>Forkhead Transcription Factors (genetics)</term><term>Gene Rearrangement</term><term>Humans</term><term>Lymphedema (genetics)</term><term>Male</term><term>Middle Aged</term><term>Mutation, Missense</term><term>Syndrome</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Cils (malformations)</term><term>Enfant</term><term>Facteurs de transcription Forkhead (génétique)</term><term>Femelle</term><term>Humains</term><term>Lymphoedème (génétique)</term><term>Mutation faux-sens</term><term>Mâle</term><term>Réarrangement des gènes</term><term>Syndrome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Forkhead Transcription Factors</term></keywords><keywords scheme="MESH" qualifier="abnormalities" xml:lang="en"><term>Eyelashes</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteurs de transcription Forkhead</term><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="malformations" xml:lang="fr"><term>Cils</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Child</term><term>Female</term><term>Gene Rearrangement</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Mutation, Missense</term><term>Syndrome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Enfant</term><term>Femelle</term><term>Humains</term><term>Mutation faux-sens</term><term>Mâle</term><term>Réarrangement des gènes</term><term>Syndrome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lymphedema-distichiasis (LD) syndrome is a rare autosomal dominant disorder of the FOXC2 gene, which codes for a forkhead transcription factor. Most of the mutations described in this gene to date are deletions or insertions, suggesting a mechanism of haploinsufficiency. We studied three independent families with LD presenting with both lymphedema and distichiasis. Two microrearrangements (one 8-bp deletion and one 7-bp duplication) occurring in a GC-rich genomic region (c.893-930) known to be prone to mutations were identified. A new missense mutation (p.Lys132Glu) located in a highly conserved sequence, the forkhead domain, was also identified. Mutations in this domain have been previously shown to impair FOXC2 transactivation ability. At a genetic level, this study confirms the heterogeneity of mutations responsible for LD and is consistent with a mechanism of haploinsufficiency. At a clinical level, it reinforces the importance of genetic testing in subjects with familial lymphedema or distichiasis, since measures can be taken at an early stage to prevent complications and to reduce the progression of lymphedema or delay its occurrence.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20552815</PMID><DateCreated><Year>2010</Year><Month>06</Month><Day>17</Day></DateCreated><DateCompleted><Year>2010</Year><Month>07</Month><Day>08</Day></DateCompleted><DateRevised><Year>2010</Year><Month>06</Month><Day>17</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0024-7766</ISSN><JournalIssue CitedMedium="Print"><Volume>43</Volume><Issue>1</Issue><PubDate><Year>2010</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Lymphology</Title><ISOAbbreviation>Lymphology</ISOAbbreviation></Journal><ArticleTitle>A novel missense mutation and two microrearrangements in the FOXC2 gene of three families with lymphedema-distichiasis syndrome.</ArticleTitle><Pagination><MedlinePgn>14-8</MedlinePgn></Pagination><Abstract><AbstractText>Lymphedema-distichiasis (LD) syndrome is a rare autosomal dominant disorder of the FOXC2 gene, which codes for a forkhead transcription factor. Most of the mutations described in this gene to date are deletions or insertions, suggesting a mechanism of haploinsufficiency. We studied three independent families with LD presenting with both lymphedema and distichiasis. Two microrearrangements (one 8-bp deletion and one 7-bp duplication) occurring in a GC-rich genomic region (c.893-930) known to be prone to mutations were identified. A new missense mutation (p.Lys132Glu) located in a highly conserved sequence, the forkhead domain, was also identified. Mutations in this domain have been previously shown to impair FOXC2 transactivation ability. At a genetic level, this study confirms the heterogeneity of mutations responsible for LD and is consistent with a mechanism of haploinsufficiency. At a clinical level, it reinforces the importance of genetic testing in subjects with familial lymphedema or distichiasis, since measures can be taken at an early stage to prevent complications and to reduce the progression of lymphedema or delay its occurrence.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fauret</LastName><ForeName>A-L</ForeName><Initials>AL</Initials><AffiliationInfo><Affiliation>Département de Génétique et Centre de Référence des Maladies Vasculaires Rares, AP-HP, Hôpital Européen Georges Pompidou Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tuleja</LastName><ForeName>E</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Jeunemaitre</LastName><ForeName>X</ForeName><Initials>X</Initials></Author><Author ValidYN="Y"><LastName>Vignes</LastName><ForeName>S</ForeName><Initials>S</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Lymphology</MedlineTA><NlmUniqueID>0155112</NlmUniqueID><ISSNLinking>0024-7766</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051858">Forkhead Transcription Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C082078">mesenchyme fork head 1 protein</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005140" MajorTopicYN="N">Eyelashes</DescriptorName><QualifierName UI="Q000002" MajorTopicYN="Y">abnormalities</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051858" MajorTopicYN="N">Forkhead Transcription Factors</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015321" MajorTopicYN="Y">Gene Rearrangement</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008209" MajorTopicYN="N">Lymphedema</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020125" MajorTopicYN="Y">Mutation, Missense</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013577" MajorTopicYN="N">Syndrome</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>6</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>6</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>7</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20552815</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>France</li></country></list><tree><noCountry><name sortKey="Jeunemaitre, X" sort="Jeunemaitre, X" uniqKey="Jeunemaitre X" first="X" last="Jeunemaitre">X. Jeunemaitre</name><name sortKey="Tuleja, E" sort="Tuleja, E" uniqKey="Tuleja E" first="E" last="Tuleja">E. Tuleja</name><name sortKey="Vignes, S" sort="Vignes, S" uniqKey="Vignes S" first="S" last="Vignes">S. Vignes</name></noCountry><country name="France"><noRegion><name sortKey="Fauret, A L" sort="Fauret, A L" uniqKey="Fauret A" first="A-L" last="Fauret">A-L Fauret</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/PubMed/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002978 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd -nk 002978 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= LymphedemaV1
|flux= PubMed
|étape= Checkpoint
|type= RBID
|clé= pubmed:20552815
|texte= A novel missense mutation and two microrearrangements in the FOXC2 gene of three families with lymphedema-distichiasis syndrome.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i -Sk "pubmed:20552815" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a LymphedemaV1
| This area was generated with Dilib version V0.6.31. |  |