Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia.
Identifieur interne : 005817 ( Main/Exploration ); précédent : 005816; suivant : 005818Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia.
Auteurs : Fiona Connell [Royaume-Uni] ; Kamini Kalidas ; Pia Ostergaard ; Glen Brice ; Tessa Homfray ; Lesley Roberts ; David J. Bunyan ; Sally Mitton ; Sahar Mansour ; Peter Mortimer (dermatologue) [Royaume-Uni] ; Steve JefferySource :
- Human genetics [ 1432-1203 ] ; 2010.
Descripteurs français
- KwdFr :
- Analyse de mutations d'ADN (), Cartographie chromosomique, Chromosomes humains de la paire 18 (génétique), Femelle, Gènes récessifs, Génotype, Humains, Issue fatale, Liaison génétique, Lymphoedème (anatomopathologie), Lymphoedème (génétique), Mort foetale, Mutation, Mâle, Nourrisson, Pedigree, Polymorphisme de nucléotide simple, Protéines de liaison au calcium (génétique), Protéines suppresseurs de tumeurs (génétique), Prédisposition génétique à une maladie (génétique), Santé de la famille, Séquence nucléotidique.
- MESH :
- anatomopathologie : Lymphoedème.
- génétique : Chromosomes humains de la paire 18, Lymphoedème, Protéines de liaison au calcium, Protéines suppresseurs de tumeurs, Prédisposition génétique à une maladie.
- Analyse de mutations d'ADN, Cartographie chromosomique, Femelle, Gènes récessifs, Génotype, Humains, Issue fatale, Liaison génétique, Mort foetale, Mutation, Mâle, Nourrisson, Pedigree, Polymorphisme de nucléotide simple, Santé de la famille, Séquence nucléotidique.
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
Affiliations:
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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 (dermatologue)</name><affiliation><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">Université de Londres</orgName></affiliation></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="KwdFr" xml:lang="fr"><term>Analyse de mutations d'ADN ()</term><term>Cartographie chromosomique</term><term>Chromosomes humains de la paire 18 (génétique)</term><term>Femelle</term><term>Gènes récessifs</term><term>Génotype</term><term>Humains</term><term>Issue fatale</term><term>Liaison génétique</term><term>Lymphoedème (anatomopathologie)</term><term>Lymphoedème (génétique)</term><term>Mort foetale</term><term>Mutation</term><term>Mâle</term><term>Nourrisson</term><term>Pedigree</term><term>Polymorphisme de nucléotide simple</term><term>Protéines de liaison au calcium (génétique)</term><term>Protéines suppresseurs de tumeurs (génétique)</term><term>Prédisposition génétique à une maladie (génétique)</term><term>Santé de la famille</term><term>Séquence nucléotidique</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="anatomopathologie" xml:lang="fr"><term>Lymphoedème</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="génétique" xml:lang="fr"><term>Chromosomes humains de la paire 18</term><term>Lymphoedème</term><term>Protéines de liaison au calcium</term><term>Protéines suppresseurs de tumeurs</term><term>Prédisposition génétique à une maladie</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><keywords scheme="MESH" xml:lang="fr"><term>Analyse de mutations d'ADN</term><term>Cartographie chromosomique</term><term>Femelle</term><term>Gènes récessifs</term><term>Génotype</term><term>Humains</term><term>Issue fatale</term><term>Liaison génétique</term><term>Mort foetale</term><term>Mutation</term><term>Mâle</term><term>Nourrisson</term><term>Pedigree</term><term>Polymorphisme de nucléotide simple</term><term>Santé de la famille</term><term>Séquence nucléotidique</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><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><noCountry><name sortKey="Brice, Glen" sort="Brice, Glen" uniqKey="Brice G" first="Glen" last="Brice">Glen Brice</name><name sortKey="Bunyan, David J" sort="Bunyan, David J" uniqKey="Bunyan D" first="David J" last="Bunyan">David J. Bunyan</name><name sortKey="Homfray, Tessa" sort="Homfray, Tessa" uniqKey="Homfray T" first="Tessa" last="Homfray">Tessa Homfray</name><name sortKey="Jeffery, Steve" sort="Jeffery, Steve" uniqKey="Jeffery S" first="Steve" last="Jeffery">Steve Jeffery</name><name sortKey="Kalidas, Kamini" sort="Kalidas, Kamini" uniqKey="Kalidas K" first="Kamini" last="Kalidas">Kamini Kalidas</name><name sortKey="Mansour, Sahar" sort="Mansour, Sahar" uniqKey="Mansour S" first="Sahar" last="Mansour">Sahar Mansour</name><name sortKey="Mitton, Sally" sort="Mitton, Sally" uniqKey="Mitton S" first="Sally" last="Mitton">Sally Mitton</name><name sortKey="Ostergaard, Pia" sort="Ostergaard, Pia" uniqKey="Ostergaard P" first="Pia" last="Ostergaard">Pia Ostergaard</name><name sortKey="Roberts, Lesley" sort="Roberts, Lesley" uniqKey="Roberts L" first="Lesley" last="Roberts">Lesley Roberts</name></noCountry><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Connell, Fiona" sort="Connell, Fiona" uniqKey="Connell F" first="Fiona" last="Connell">Fiona Connell</name></region><name sortKey="Mortimer, Peter" sort="Mortimer, Peter" uniqKey="Mortimer P" first="Peter" last="Mortimer">Peter Mortimer (dermatologue)</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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