Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia.
Identifieur interne : 002C82 ( PubMed/Corpus ); précédent : 002C81; suivant : 002C83Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia.
Auteurs : Fiona Connell ; Kamini Kalidas ; Pia Ostergaard ; Glen Brice ; Tessa Homfray ; Lesley Roberts ; David J. Bunyan ; Sally Mitton ; Sahar Mansour ; Peter Mortimer ; Steve JefferySource :
- Human genetics [ 1432-1203 ] ; 2010.
English descriptors
- KwdEn :
- Base Sequence, Calcium-Binding Proteins (genetics), Chromosome Mapping, Chromosomes, Human, Pair 18 (genetics), DNA Mutational Analysis (methods), Family Health, Fatal Outcome, Female, Fetal Death, Genes, Recessive, Genetic Linkage, Genetic Predisposition to Disease (genetics), Genotype, Humans, Infant, Lymphedema (genetics), Lymphedema (pathology), Male, Mutation, Pedigree, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins (genetics).
- MESH :
- chemical , genetics : Calcium-Binding Proteins, Tumor Suppressor Proteins.
- genetics : Chromosomes, Human, Pair 18, Genetic Predisposition to Disease, Lymphedema.
- methods : DNA Mutational Analysis.
- pathology : Lymphedema.
- Base Sequence, Chromosome Mapping, Family Health, Fatal Outcome, Female, Fetal Death, Genes, Recessive, Genetic Linkage, Genotype, Humans, Infant, Male, Mutation, Pedigree, Polymorphism, Single Nucleotide.
Abstract
Generalised lymphatic dysplasia (GLD) is characterised by extensive peripheral lymphoedema with visceral involvement. In some cases, it presents in utero with hydrops fetalis. Autosomal dominant and recessive inheritance has been reported. A large, non-consanguineous family with three affected siblings with generalised lymphatic dysplasia is presented. One child died aged 5 months, one spontaneously miscarried at 17 weeks gestation, and the third has survived with extensive lymphoedema. All three presented with hydrops fetalis. There are seven other siblings who are clinically unaffected. Linkage analysis produced two loci on chromosome 18, covering 22 Mb and containing 150 genes, one of which is CCBE1. A homozygous cysteine to serine change in CCBE1 has been identified in the proband, in a residue that is conserved across species. High density SNP analysis revealed homozygosity (a region of 900 kb) around the locus for CCBE1 in all three affected cases. This indicates a likely ancestral mutation that is common to both parents; an example of a homozygous mutation representing Identity by Descent (IBD) in this pedigree. Recent studies in zebrafish have shown this gene to be required for lymphangiogenesis and venous sprouting and are therefore supportive of our findings. In view of the conserved nature of the cysteine, the nature of the amino acid change, the occurrence of a homozygous region around the locus, the segregation within the family, and the evidence from zebrafish, we propose that this mutation is causative for the generalised lymphatic dysplasia in this family, and may be of relevance in cases of non-immune hydrops fetalis.
DOI: 10.1007/s00439-009-0766-y
PubMed: 19911200
Links to Exploration step
pubmed:19911200Le document en format XML
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Bunyan</name></author><author><name sortKey="Mitton, Sally" sort="Mitton, Sally" uniqKey="Mitton S" first="Sally" last="Mitton">Sally Mitton</name></author><author><name sortKey="Mansour, Sahar" sort="Mansour, Sahar" uniqKey="Mansour S" first="Sahar" last="Mansour">Sahar Mansour</name></author><author><name sortKey="Mortimer, Peter" sort="Mortimer, Peter" uniqKey="Mortimer P" first="Peter" last="Mortimer">Peter Mortimer</name></author><author><name sortKey="Jeffery, Steve" sort="Jeffery, Steve" uniqKey="Jeffery S" first="Steve" last="Jeffery">Steve Jeffery</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2010">2010</date><idno type="RBID">pubmed:19911200</idno><idno type="pmid">19911200</idno><idno type="doi">10.1007/s00439-009-0766-y</idno><idno type="wicri:Area/PubMed/Corpus">002C82</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002C82</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia.</title><author><name sortKey="Connell, Fiona" sort="Connell, Fiona" uniqKey="Connell F" first="Fiona" last="Connell">Fiona Connell</name><affiliation><nlm:affiliation>Medical Genetics Unit, Clinical Developmental Sciences, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Kalidas, Kamini" sort="Kalidas, Kamini" uniqKey="Kalidas K" first="Kamini" last="Kalidas">Kamini Kalidas</name></author><author><name sortKey="Ostergaard, Pia" sort="Ostergaard, Pia" uniqKey="Ostergaard P" first="Pia" last="Ostergaard">Pia Ostergaard</name></author><author><name sortKey="Brice, Glen" sort="Brice, Glen" uniqKey="Brice G" first="Glen" last="Brice">Glen Brice</name></author><author><name sortKey="Homfray, Tessa" sort="Homfray, Tessa" uniqKey="Homfray T" first="Tessa" last="Homfray">Tessa Homfray</name></author><author><name sortKey="Roberts, Lesley" sort="Roberts, Lesley" uniqKey="Roberts L" first="Lesley" last="Roberts">Lesley Roberts</name></author><author><name sortKey="Bunyan, David J" sort="Bunyan, David J" uniqKey="Bunyan D" first="David J" last="Bunyan">David J. Bunyan</name></author><author><name sortKey="Mitton, Sally" sort="Mitton, Sally" uniqKey="Mitton S" first="Sally" last="Mitton">Sally Mitton</name></author><author><name sortKey="Mansour, Sahar" sort="Mansour, Sahar" uniqKey="Mansour S" first="Sahar" last="Mansour">Sahar Mansour</name></author><author><name sortKey="Mortimer, Peter" sort="Mortimer, Peter" uniqKey="Mortimer P" first="Peter" last="Mortimer">Peter Mortimer</name></author><author><name sortKey="Jeffery, Steve" sort="Jeffery, Steve" uniqKey="Jeffery S" first="Steve" last="Jeffery">Steve Jeffery</name></author></analytic><series><title level="j">Human genetics</title><idno type="eISSN">1432-1203</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Base Sequence</term><term>Calcium-Binding Proteins (genetics)</term><term>Chromosome Mapping</term><term>Chromosomes, Human, Pair 18 (genetics)</term><term>DNA Mutational Analysis (methods)</term><term>Family Health</term><term>Fatal Outcome</term><term>Female</term><term>Fetal Death</term><term>Genes, Recessive</term><term>Genetic Linkage</term><term>Genetic Predisposition to Disease (genetics)</term><term>Genotype</term><term>Humans</term><term>Infant</term><term>Lymphedema (genetics)</term><term>Lymphedema (pathology)</term><term>Male</term><term>Mutation</term><term>Pedigree</term><term>Polymorphism, Single Nucleotide</term><term>Tumor Suppressor Proteins (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Calcium-Binding Proteins</term><term>Tumor Suppressor Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Chromosomes, Human, Pair 18</term><term>Genetic Predisposition to Disease</term><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>DNA Mutational Analysis</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Base Sequence</term><term>Chromosome Mapping</term><term>Family Health</term><term>Fatal Outcome</term><term>Female</term><term>Fetal Death</term><term>Genes, Recessive</term><term>Genetic Linkage</term><term>Genotype</term><term>Humans</term><term>Infant</term><term>Male</term><term>Mutation</term><term>Pedigree</term><term>Polymorphism, Single Nucleotide</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Generalised lymphatic dysplasia (GLD) is characterised by extensive peripheral lymphoedema with visceral involvement. In some cases, it presents in utero with hydrops fetalis. Autosomal dominant and recessive inheritance has been reported. A large, non-consanguineous family with three affected siblings with generalised lymphatic dysplasia is presented. One child died aged 5 months, one spontaneously miscarried at 17 weeks gestation, and the third has survived with extensive lymphoedema. All three presented with hydrops fetalis. There are seven other siblings who are clinically unaffected. Linkage analysis produced two loci on chromosome 18, covering 22 Mb and containing 150 genes, one of which is CCBE1. A homozygous cysteine to serine change in CCBE1 has been identified in the proband, in a residue that is conserved across species. High density SNP analysis revealed homozygosity (a region of 900 kb) around the locus for CCBE1 in all three affected cases. This indicates a likely ancestral mutation that is common to both parents; an example of a homozygous mutation representing Identity by Descent (IBD) in this pedigree. Recent studies in zebrafish have shown this gene to be required for lymphangiogenesis and venous sprouting and are therefore supportive of our findings. In view of the conserved nature of the cysteine, the nature of the amino acid change, the occurrence of a homozygous region around the locus, the segregation within the family, and the evidence from zebrafish, we propose that this mutation is causative for the generalised lymphatic dysplasia in this family, and may be of relevance in cases of non-immune hydrops fetalis.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">19911200</PMID><DateCreated><Year>2010</Year><Month>01</Month><Day>21</Day></DateCreated><DateCompleted><Year>2010</Year><Month>02</Month><Day>12</Day></DateCompleted><DateRevised><Year>2010</Year><Month>11</Month><Day>18</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1432-1203</ISSN><JournalIssue CitedMedium="Internet"><Volume>127</Volume><Issue>2</Issue><PubDate><Year>2010</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Human genetics</Title><ISOAbbreviation>Hum. Genet.</ISOAbbreviation></Journal><ArticleTitle>Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia.</ArticleTitle><Pagination><MedlinePgn>231-41</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s00439-009-0766-y</ELocationID><Abstract><AbstractText>Generalised lymphatic dysplasia (GLD) is characterised by extensive peripheral lymphoedema with visceral involvement. In some cases, it presents in utero with hydrops fetalis. Autosomal dominant and recessive inheritance has been reported. A large, non-consanguineous family with three affected siblings with generalised lymphatic dysplasia is presented. One child died aged 5 months, one spontaneously miscarried at 17 weeks gestation, and the third has survived with extensive lymphoedema. All three presented with hydrops fetalis. There are seven other siblings who are clinically unaffected. Linkage analysis produced two loci on chromosome 18, covering 22 Mb and containing 150 genes, one of which is CCBE1. A homozygous cysteine to serine change in CCBE1 has been identified in the proband, in a residue that is conserved across species. High density SNP analysis revealed homozygosity (a region of 900 kb) around the locus for CCBE1 in all three affected cases. This indicates a likely ancestral mutation that is common to both parents; an example of a homozygous mutation representing Identity by Descent (IBD) in this pedigree. Recent studies in zebrafish have shown this gene to be required for lymphangiogenesis and venous sprouting and are therefore supportive of our findings. In view of the conserved nature of the cysteine, the nature of the amino acid change, the occurrence of a homozygous region around the locus, the segregation within the family, and the evidence from zebrafish, we propose that this mutation is causative for the generalised lymphatic dysplasia in this family, and may be of relevance in cases of non-immune hydrops fetalis.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Connell</LastName><ForeName>Fiona</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Medical Genetics Unit, Clinical Developmental Sciences, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kalidas</LastName><ForeName>Kamini</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Ostergaard</LastName><ForeName>Pia</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Brice</LastName><ForeName>Glen</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Homfray</LastName><ForeName>Tessa</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Roberts</LastName><ForeName>Lesley</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Bunyan</LastName><ForeName>David J</ForeName><Initials>DJ</Initials></Author><Author ValidYN="Y"><LastName>Mitton</LastName><ForeName>Sally</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Mansour</LastName><ForeName>Sahar</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Mortimer</LastName><ForeName>Peter</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Jeffery</LastName><ForeName>Steve</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><CollectiveName>Lymphoedema Consortium</CollectiveName></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><Agency>British Heart Foundation</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>11</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Hum Genet</MedlineTA><NlmUniqueID>7613873</NlmUniqueID><ISSNLinking>0340-6717</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C546964">CCBE1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002135">Calcium-Binding Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D025521">Tumor Suppressor Proteins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="ErratumIn"><RefSource>Hum Genet. 2010 Feb;127(2):243</RefSource></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D001483" MajorTopicYN="N">Base Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002135" MajorTopicYN="N">Calcium-Binding Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002874" MajorTopicYN="N">Chromosome Mapping</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002887" MajorTopicYN="N">Chromosomes, Human, Pair 18</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004252" MajorTopicYN="N">DNA Mutational Analysis</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005192" MajorTopicYN="N">Family Health</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017809" MajorTopicYN="N">Fatal Outcome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005313" MajorTopicYN="N">Fetal Death</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005808" MajorTopicYN="N">Genes, Recessive</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008040" MajorTopicYN="Y">Genetic Linkage</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005838" MajorTopicYN="N">Genotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007223" MajorTopicYN="N">Infant</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008209" MajorTopicYN="N">Lymphedema</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="Y">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010375" MajorTopicYN="N">Pedigree</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020641" MajorTopicYN="N">Polymorphism, Single Nucleotide</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D025521" MajorTopicYN="N">Tumor Suppressor Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2009</Year><Month>09</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2009</Year><Month>11</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2009</Year><Month>11</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2009</Year><Month>11</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>2</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">19911200</ArticleId><ArticleId IdType="doi">10.1007/s00439-009-0766-y</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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