Clinical and genetic study of 46 Italian patients with primary lymphedema.
Identifieur interne : 002049 ( PubMed/Curation ); précédent : 002048; suivant : 002050Clinical and genetic study of 46 Italian patients with primary lymphedema.
Auteurs : S. Michelini [Italie] ; D. Degiorgio ; M. Cestari ; D. Corda ; M. Ricci ; M. Cardone ; A. Mander ; L. Famoso ; E. Contini ; R. Serrani ; L. Pinelli ; S. Cecchin ; M. BertelliSource :
- Lymphology [ 0024-7766 ] ; 2012.
Descripteurs français
- KwdFr :
- Analyse de mutations d'ADN, Exons, Facteurs de transcription Forkhead (génétique), Femelle, Humains, Italie, Jeune adulte, Lymphangiogenèse (génétique), Lymphoedème (anatomopathologie), Lymphoedème (génétique), Lymphoedème (physiopathologie), Mutation, Mâle, Phénotype, Prédisposition génétique à une maladie, Réaction de polymérisation en chaîne, Récepteur-3 au facteur croissance endothéliale vasculaire (génétique), Âge de début, Études cas-témoins.
- MESH :
- anatomopathologie : Lymphoedème.
- génétique : Facteurs de transcription Forkhead, Lymphangiogenèse, Lymphoedème, Récepteur-3 au facteur croissance endothéliale vasculaire.
- physiopathologie : Lymphoedème.
- Analyse de mutations d'ADN, Exons, Femelle, Humains, Italie, Jeune adulte, Mutation, Mâle, Phénotype, Prédisposition génétique à une maladie, Réaction de polymérisation en chaîne, Âge de début, Études cas-témoins.
- Wicri :
- geographic : Italie.
English descriptors
- KwdEn :
- Age of Onset, Case-Control Studies, DNA Mutational Analysis, Exons, Female, Forkhead Transcription Factors (genetics), Genetic Predisposition to Disease, Humans, Italy, Lymphangiogenesis (genetics), Lymphedema (genetics), Lymphedema (pathology), Lymphedema (physiopathology), Male, Mutation, Phenotype, Polymerase Chain Reaction, Vascular Endothelial Growth Factor Receptor-3 (genetics), Young Adult.
- MESH :
- chemical , genetics : Forkhead Transcription Factors, Vascular Endothelial Growth Factor Receptor-3.
- geographic : Italy.
- genetics : Lymphangiogenesis, Lymphedema.
- pathology : Lymphedema.
- physiopathology : Lymphedema.
- Age of Onset, Case-Control Studies, DNA Mutational Analysis, Exons, Female, Genetic Predisposition to Disease, Humans, Male, Mutation, Phenotype, Polymerase Chain Reaction, Young Adult.
Abstract
Primary lymphedema is characterized by altered morphological development of lymphatic vessels causing fluid accumulation in interstitial spaces. In familial forms, it is primarily transmitted as a dominant Mendelian trait with heterozygous mutations in genes involved in lymphangiogenesis. We used PCR and direct sequencing to analyze the region of the fms-related tyrosine kinase 4 (FLT4) gene encoding the "tyrosine-kinase domain" and the single exon of the forkhead box C2 (FOXC2) gene in 46 Italian probands with primary lymphedema, 42 of whom had familial forms. We identified 12 mutations in 12 patients (12/46, 26%), six in the FLT4 gene and six in the FOXC2 gene. Most of the mutations (9/12, 75%) were new, and none were identified in 100 healthy subjects or listed in the NCBI dbSNP. A clear relation emerged between genotype and phenotype because 4/5 (80%) probands with onset at birth showed FLT4 mutations and 4/5 (80%) probands without distichiasis and with FOXC2 mutations had an amino-acid substitution outside the forkhead domain. Besides the allelic heterogeneity shown by unique mutations in each proband, the absence of mutations in almost 75% of familial cases of primary lymphedema also suggests genetic heterogeneity.
PubMed: 22768468
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Corda</name></author><author><name sortKey="Ricci, M" sort="Ricci, M" uniqKey="Ricci M" first="M" last="Ricci">M. Ricci</name></author><author><name sortKey="Cardone, M" sort="Cardone, M" uniqKey="Cardone M" first="M" last="Cardone">M. Cardone</name></author><author><name sortKey="Mander, A" sort="Mander, A" uniqKey="Mander A" first="A" last="Mander">A. Mander</name></author><author><name sortKey="Famoso, L" sort="Famoso, L" uniqKey="Famoso L" first="L" last="Famoso">L. Famoso</name></author><author><name sortKey="Contini, E" sort="Contini, E" uniqKey="Contini E" first="E" last="Contini">E. Contini</name></author><author><name sortKey="Serrani, R" sort="Serrani, R" uniqKey="Serrani R" first="R" last="Serrani">R. Serrani</name></author><author><name sortKey="Pinelli, L" sort="Pinelli, L" uniqKey="Pinelli L" first="L" last="Pinelli">L. Pinelli</name></author><author><name sortKey="Cecchin, S" sort="Cecchin, S" uniqKey="Cecchin S" first="S" last="Cecchin">S. 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Cardone</name></author><author><name sortKey="Mander, A" sort="Mander, A" uniqKey="Mander A" first="A" last="Mander">A. Mander</name></author><author><name sortKey="Famoso, L" sort="Famoso, L" uniqKey="Famoso L" first="L" last="Famoso">L. Famoso</name></author><author><name sortKey="Contini, E" sort="Contini, E" uniqKey="Contini E" first="E" last="Contini">E. Contini</name></author><author><name sortKey="Serrani, R" sort="Serrani, R" uniqKey="Serrani R" first="R" last="Serrani">R. Serrani</name></author><author><name sortKey="Pinelli, L" sort="Pinelli, L" uniqKey="Pinelli L" first="L" last="Pinelli">L. Pinelli</name></author><author><name sortKey="Cecchin, S" sort="Cecchin, S" uniqKey="Cecchin S" first="S" last="Cecchin">S. Cecchin</name></author><author><name sortKey="Bertelli, M" sort="Bertelli, M" uniqKey="Bertelli M" first="M" last="Bertelli">M. Bertelli</name></author></analytic><series><title level="j">Lymphology</title><idno type="ISSN">0024-7766</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Age of Onset</term><term>Case-Control Studies</term><term>DNA Mutational Analysis</term><term>Exons</term><term>Female</term><term>Forkhead Transcription Factors (genetics)</term><term>Genetic Predisposition to Disease</term><term>Humans</term><term>Italy</term><term>Lymphangiogenesis (genetics)</term><term>Lymphedema (genetics)</term><term>Lymphedema (pathology)</term><term>Lymphedema (physiopathology)</term><term>Male</term><term>Mutation</term><term>Phenotype</term><term>Polymerase Chain Reaction</term><term>Vascular Endothelial Growth Factor Receptor-3 (genetics)</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de mutations d'ADN</term><term>Exons</term><term>Facteurs de transcription Forkhead (génétique)</term><term>Femelle</term><term>Humains</term><term>Italie</term><term>Jeune adulte</term><term>Lymphangiogenèse (génétique)</term><term>Lymphoedème (anatomopathologie)</term><term>Lymphoedème (génétique)</term><term>Lymphoedème (physiopathologie)</term><term>Mutation</term><term>Mâle</term><term>Phénotype</term><term>Prédisposition génétique à une maladie</term><term>Réaction de polymérisation en chaîne</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire (génétique)</term><term>Âge de début</term><term>Études cas-témoins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Forkhead Transcription Factors</term><term>Vascular Endothelial Growth Factor Receptor-3</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>Italy</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Lymphangiogenesis</term><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteurs de transcription Forkhead</term><term>Lymphangiogenèse</term><term>Lymphoedème</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Age of Onset</term><term>Case-Control Studies</term><term>DNA Mutational Analysis</term><term>Exons</term><term>Female</term><term>Genetic Predisposition to Disease</term><term>Humans</term><term>Male</term><term>Mutation</term><term>Phenotype</term><term>Polymerase Chain Reaction</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de mutations d'ADN</term><term>Exons</term><term>Femelle</term><term>Humains</term><term>Italie</term><term>Jeune adulte</term><term>Mutation</term><term>Mâle</term><term>Phénotype</term><term>Prédisposition génétique à une maladie</term><term>Réaction de polymérisation en chaîne</term><term>Âge de début</term><term>Études cas-témoins</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Italie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Primary lymphedema is characterized by altered morphological development of lymphatic vessels causing fluid accumulation in interstitial spaces. In familial forms, it is primarily transmitted as a dominant Mendelian trait with heterozygous mutations in genes involved in lymphangiogenesis. We used PCR and direct sequencing to analyze the region of the fms-related tyrosine kinase 4 (FLT4) gene encoding the "tyrosine-kinase domain" and the single exon of the forkhead box C2 (FOXC2) gene in 46 Italian probands with primary lymphedema, 42 of whom had familial forms. We identified 12 mutations in 12 patients (12/46, 26%), six in the FLT4 gene and six in the FOXC2 gene. Most of the mutations (9/12, 75%) were new, and none were identified in 100 healthy subjects or listed in the NCBI dbSNP. A clear relation emerged between genotype and phenotype because 4/5 (80%) probands with onset at birth showed FLT4 mutations and 4/5 (80%) probands without distichiasis and with FOXC2 mutations had an amino-acid substitution outside the forkhead domain. Besides the allelic heterogeneity shown by unique mutations in each proband, the absence of mutations in almost 75% of familial cases of primary lymphedema also suggests genetic heterogeneity.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">22768468</PMID><DateCreated><Year>2012</Year><Month>07</Month><Day>06</Day></DateCreated><DateCompleted><Year>2012</Year><Month>07</Month><Day>24</Day></DateCompleted><DateRevised><Year>2012</Year><Month>10</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0024-7766</ISSN><JournalIssue CitedMedium="Print"><Volume>45</Volume><Issue>1</Issue><PubDate><Year>2012</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Lymphology</Title><ISOAbbreviation>Lymphology</ISOAbbreviation></Journal><ArticleTitle>Clinical and genetic study of 46 Italian patients with primary lymphedema.</ArticleTitle><Pagination><MedlinePgn>3-12</MedlinePgn></Pagination><Abstract><AbstractText>Primary lymphedema is characterized by altered morphological development of lymphatic vessels causing fluid accumulation in interstitial spaces. In familial forms, it is primarily transmitted as a dominant Mendelian trait with heterozygous mutations in genes involved in lymphangiogenesis. We used PCR and direct sequencing to analyze the region of the fms-related tyrosine kinase 4 (FLT4) gene encoding the "tyrosine-kinase domain" and the single exon of the forkhead box C2 (FOXC2) gene in 46 Italian probands with primary lymphedema, 42 of whom had familial forms. We identified 12 mutations in 12 patients (12/46, 26%), six in the FLT4 gene and six in the FOXC2 gene. Most of the mutations (9/12, 75%) were new, and none were identified in 100 healthy subjects or listed in the NCBI dbSNP. A clear relation emerged between genotype and phenotype because 4/5 (80%) probands with onset at birth showed FLT4 mutations and 4/5 (80%) probands without distichiasis and with FOXC2 mutations had an amino-acid substitution outside the forkhead domain. Besides the allelic heterogeneity shown by unique mutations in each proband, the absence of mutations in almost 75% of familial cases of primary lymphedema also suggests genetic heterogeneity.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Michelini</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Vascular Rehabilitation, San Giovanni Battista Hospital, Rome, Italy. s.michelini@acismom.it</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Degiorgio</LastName><ForeName>D</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Cestari</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Corda</LastName><ForeName>D</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Ricci</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Cardone</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Mander</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Famoso</LastName><ForeName>L</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Contini</LastName><ForeName>E</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Serrani</LastName><ForeName>R</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Pinelli</LastName><ForeName>L</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Cecchin</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Bertelli</LastName><ForeName>M</ForeName><Initials>M</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</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><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D040321">Vascular Endothelial Growth Factor Receptor-3</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Lymphology. 2012 Mar;45(1):1-2</RefSource><PMID Version="1">22768467</PMID></CommentsCorrections><CommentsCorrections RefType="ErratumIn"><RefSource>Lymphology. 2012 Jun;45(2):87</RefSource></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D017668" MajorTopicYN="N">Age of Onset</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016022" MajorTopicYN="N">Case-Control Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004252" MajorTopicYN="N">DNA Mutational Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005091" MajorTopicYN="N">Exons</DescriptorName></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="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007558" MajorTopicYN="N" Type="Geographic">Italy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D042583" MajorTopicYN="N">Lymphangiogenesis</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008209" MajorTopicYN="N">Lymphedema</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="Y">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010641" MajorTopicYN="N">Phenotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016133" MajorTopicYN="N">Polymerase Chain Reaction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D040321" MajorTopicYN="N">Vascular Endothelial Growth Factor Receptor-3</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>7</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>7</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>7</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">22768468</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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