Recurrent Mutations in a Single Exon Encoding the Evolutionarily Conserved Olfactomedin-Homology Domain of TIGR in Familial Open-Angle Glaucoma
Identifieur interne : 002242 ( Istex/Corpus ); précédent : 002241; suivant : 002243Recurrent Mutations in a Single Exon Encoding the Evolutionarily Conserved Olfactomedin-Homology Domain of TIGR in Familial Open-Angle Glaucoma
Auteurs : Marie F. Adam ; Ahmed Belmouden ; Philippe Binisti ; Antoine P. Brézin ; Françoise Valtot ; Alain Béchetoille ; Jean-Claude Dascotte ; Bruno Copin ; Lucienne Gomez ; André Chaventré ; Jean-François Bach ; Henri-Jean GarchonSource :
- Human Molecular Genetics [ 0964-6906 ] ; 1997-11.
Abstract
Primary open-angle glaucoma (POAG) is a highly prevalent cause of irreversible blindness which associates cupping of the optic disc and alteration of the visual field, elevation of intraocular pressure being a major risk factor. Provided diagnosis is made at an early stage, treatments are available to prevent visual impairment. A locus, GLC1A, has been mapped on chromosome 1q23ȓq25 in several families affected with juvenile-onset POAG (JOAG) and also in some families affected with juvenile and middle-age onset POAG. Recently, three mutations of the TIGR (Trabecular meshwork-Induced Glucocorticoid Response) gene were shown to be responsible for the disease in several American families and in unrelated POAG patients. We now describe five new mutations in eight French families. All mutations known to date appear to concentrate in the evolutionarily conserved C-terminal domain of TIGR which bears homology to frog olfactomedin, an extracellular matrix glycoprotein of the olfactory epithelium, to rat and human neuronal olfactomedin-related proteins and to F11C3.2, a protein from Caenorhabditis elegans. Moreover, this conserved domain of TIGR is encoded by a single exon to which mutation screening could be limited. Surprisingly, the TIGR message, which is abundantly transcribed in the trabecular meshwork and also in the ciliary body and the sclera, is not expressed in the optic nerve whose degeneration is, however, the primary lesion of POAG.
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DOI: 10.1093/hmg/6.12.2091
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Adam</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Belmouden, Ahmed" sort="Belmouden, Ahmed" uniqKey="Belmouden A" first="Ahmed" last="Belmouden">Ahmed Belmouden</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Binisti, Philippe" sort="Binisti, Philippe" uniqKey="Binisti P" first="Philippe" last="Binisti">Philippe Binisti</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Brezin, Antoine P" sort="Brezin, Antoine P" uniqKey="Brezin A" first="Antoine P." last="Brézin">Antoine P. Brézin</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Valtot, Francoise" sort="Valtot, Francoise" uniqKey="Valtot F" first="Françoise" last="Valtot">Françoise Valtot</name><affiliation><mods:affiliation>Institut du Glaucome, Hopital Saint-Joseph, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Bechetoille, Alain" sort="Bechetoille, Alain" uniqKey="Bechetoille A" first="Alain" last="Béchetoille">Alain Béchetoille</name><affiliation><mods:affiliation>Service d'Ophtalmologie, C.H.U. Angers, Angers, France</mods:affiliation></affiliation></author><author><name sortKey="Dascotte, Jean Claude" sort="Dascotte, Jean Claude" uniqKey="Dascotte J" first="Jean-Claude" last="Dascotte">Jean-Claude Dascotte</name><affiliation><mods:affiliation>Service d'Ophtalmologie, C.H.U. Lille, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Copin, Bruno" sort="Copin, Bruno" uniqKey="Copin B" first="Bruno" last="Copin">Bruno Copin</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Gomez, Lucienne" sort="Gomez, Lucienne" uniqKey="Gomez L" first="Lucienne" last="Gomez">Lucienne Gomez</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Chaventre, Andre" sort="Chaventre, Andre" uniqKey="Chaventre A" first="André" last="Chaventré">André Chaventré</name><affiliation><mods:affiliation>Laboratoire d'Anthropologie et de Démographie Génétiques, Université Bordeaux 2, Bordeaux, France</mods:affiliation></affiliation></author><author><name sortKey="Bach, Jean Francois" sort="Bach, Jean Francois" uniqKey="Bach J" first="Jean-François" last="Bach">Jean-François Bach</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Garchon, Henri Jean" sort="Garchon, Henri Jean" uniqKey="Garchon H" first="Henri-Jean" last="Garchon">Henri-Jean Garchon</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: garchon@necker.fr</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889</idno><date when="1997" year="1997">1997</date><idno type="doi">10.1093/hmg/6.12.2091</idno><idno type="url">https://api.istex.fr/document/8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">002242</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002242</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Recurrent Mutations in a Single Exon Encoding the Evolutionarily Conserved Olfactomedin-Homology Domain of TIGR in Familial Open-Angle Glaucoma</title><author><name sortKey="Adam, Marie F" sort="Adam, Marie F" uniqKey="Adam M" first="Marie F." last="Adam">Marie F. Adam</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Belmouden, Ahmed" sort="Belmouden, Ahmed" uniqKey="Belmouden A" first="Ahmed" last="Belmouden">Ahmed Belmouden</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Binisti, Philippe" sort="Binisti, Philippe" uniqKey="Binisti P" first="Philippe" last="Binisti">Philippe Binisti</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Brezin, Antoine P" sort="Brezin, Antoine P" uniqKey="Brezin A" first="Antoine P." last="Brézin">Antoine P. Brézin</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Valtot, Francoise" sort="Valtot, Francoise" uniqKey="Valtot F" first="Françoise" last="Valtot">Françoise Valtot</name><affiliation><mods:affiliation>Institut du Glaucome, Hopital Saint-Joseph, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Bechetoille, Alain" sort="Bechetoille, Alain" uniqKey="Bechetoille A" first="Alain" last="Béchetoille">Alain Béchetoille</name><affiliation><mods:affiliation>Service d'Ophtalmologie, C.H.U. Angers, Angers, France</mods:affiliation></affiliation></author><author><name sortKey="Dascotte, Jean Claude" sort="Dascotte, Jean Claude" uniqKey="Dascotte J" first="Jean-Claude" last="Dascotte">Jean-Claude Dascotte</name><affiliation><mods:affiliation>Service d'Ophtalmologie, C.H.U. Lille, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Copin, Bruno" sort="Copin, Bruno" uniqKey="Copin B" first="Bruno" last="Copin">Bruno Copin</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Gomez, Lucienne" sort="Gomez, Lucienne" uniqKey="Gomez L" first="Lucienne" last="Gomez">Lucienne Gomez</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Chaventre, Andre" sort="Chaventre, Andre" uniqKey="Chaventre A" first="André" last="Chaventré">André Chaventré</name><affiliation><mods:affiliation>Laboratoire d'Anthropologie et de Démographie Génétiques, Université Bordeaux 2, Bordeaux, France</mods:affiliation></affiliation></author><author><name sortKey="Bach, Jean Francois" sort="Bach, Jean Francois" uniqKey="Bach J" first="Jean-François" last="Bach">Jean-François Bach</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation></author><author><name sortKey="Garchon, Henri Jean" sort="Garchon, Henri Jean" uniqKey="Garchon H" first="Henri-Jean" last="Garchon">Henri-Jean Garchon</name><affiliation><mods:affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: garchon@necker.fr</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><title level="j" type="abbrev">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="1997-11">1997-11</date><biblScope unit="volume">6</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="2091">2091</biblScope><biblScope unit="page" to="2097">2097</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889</idno><idno type="DOI">10.1093/hmg/6.12.2091</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Primary open-angle glaucoma (POAG) is a highly prevalent cause of irreversible blindness which associates cupping of the optic disc and alteration of the visual field, elevation of intraocular pressure being a major risk factor. Provided diagnosis is made at an early stage, treatments are available to prevent visual impairment. A locus, GLC1A, has been mapped on chromosome 1q23ȓq25 in several families affected with juvenile-onset POAG (JOAG) and also in some families affected with juvenile and middle-age onset POAG. Recently, three mutations of the TIGR (Trabecular meshwork-Induced Glucocorticoid Response) gene were shown to be responsible for the disease in several American families and in unrelated POAG patients. We now describe five new mutations in eight French families. All mutations known to date appear to concentrate in the evolutionarily conserved C-terminal domain of TIGR which bears homology to frog olfactomedin, an extracellular matrix glycoprotein of the olfactory epithelium, to rat and human neuronal olfactomedin-related proteins and to F11C3.2, a protein from Caenorhabditis elegans. Moreover, this conserved domain of TIGR is encoded by a single exon to which mutation screening could be limited. Surprisingly, the TIGR message, which is abundantly transcribed in the trabecular meshwork and also in the ciliary body and the sclera, is not expressed in the optic nerve whose degeneration is, however, the primary lesion of POAG.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Marie F. Adam</name><affiliations><json:string>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</json:string></affiliations></json:item><json:item><name>Ahmed Belmouden</name><affiliations><json:string>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</json:string></affiliations></json:item><json:item><name>Philippe Binisti</name><affiliations><json:string>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</json:string></affiliations></json:item><json:item><name>Antoine P. Brézin</name><affiliations><json:string>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</json:string></affiliations></json:item><json:item><name>Françoise Valtot</name><affiliations><json:string>Institut du Glaucome, Hopital Saint-Joseph, Paris, France</json:string></affiliations></json:item><json:item><name>Alain Béchetoille</name><affiliations><json:string>Service d'Ophtalmologie, C.H.U. Angers, Angers, France</json:string></affiliations></json:item><json:item><name>Jean-Claude Dascotte</name><affiliations><json:string>Service d'Ophtalmologie, C.H.U. Lille, Lille, France</json:string></affiliations></json:item><json:item><name>Bruno Copin</name><affiliations><json:string>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</json:string></affiliations></json:item><json:item><name>Lucienne Gomez</name><affiliations><json:string>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</json:string></affiliations></json:item><json:item><name>André Chaventré</name><affiliations><json:string>Laboratoire d'Anthropologie et de Démographie Génétiques, Université Bordeaux 2, Bordeaux, France</json:string></affiliations></json:item><json:item><name>Jean-François Bach</name><affiliations><json:string>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</json:string></affiliations></json:item><json:item><name>Henri-Jean Garchon</name><affiliations><json:string>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</json:string><json:string>E-mail: garchon@necker.fr</json:string></affiliations></json:item></author><language><json:string>unknown</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Primary open-angle glaucoma (POAG) is a highly prevalent cause of irreversible blindness which associates cupping of the optic disc and alteration of the visual field, elevation of intraocular pressure being a major risk factor. Provided diagnosis is made at an early stage, treatments are available to prevent visual impairment. A locus, GLC1A, has been mapped on chromosome 1q23ȓq25 in several families affected with juvenile-onset POAG (JOAG) and also in some families affected with juvenile and middle-age onset POAG. Recently, three mutations of the TIGR (Trabecular meshwork-Induced Glucocorticoid Response) gene were shown to be responsible for the disease in several American families and in unrelated POAG patients. We now describe five new mutations in eight French families. All mutations known to date appear to concentrate in the evolutionarily conserved C-terminal domain of TIGR which bears homology to frog olfactomedin, an extracellular matrix glycoprotein of the olfactory epithelium, to rat and human neuronal olfactomedin-related proteins and to F11C3.2, a protein from Caenorhabditis elegans. Moreover, this conserved domain of TIGR is encoded by a single exon to which mutation screening could be limited. Surprisingly, the TIGR message, which is abundantly transcribed in the trabecular meshwork and also in the ciliary body and the sclera, is not expressed in the optic nerve whose degeneration is, however, the primary lesion of POAG.</abstract><qualityIndicators><score>8.735</score><pdfVersion>1.2</pdfVersion><pdfPageSize>595 x 842 pts (A4)</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1459</abstractCharCount><pdfWordCount>4131</pdfWordCount><pdfCharCount>26818</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>217</abstractWordCount></qualityIndicators><title>Recurrent Mutations in a Single Exon Encoding the Evolutionarily Conserved Olfactomedin-Homology Domain of TIGR in Familial Open-Angle Glaucoma</title><refBibs><json:item><author><json:item><name>M.C. Leske</name></json:item></author><host><volume>118</volume><pages><last>191</last><first>166</first></pages><author></author><title>Am. J. 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Biochem.</title></host><title>Single-step method of RNA isolation by acid-guanidinium-thiocyanate-phenol-chloroform extraction</title></json:item></refBibs><genre><json:string>research-article</json:string></genre><host><volume>6</volume><publisherId><json:string>hmg</json:string></publisherId><pages><last>2097</last><first>2091</first></pages><issn><json:string>0964-6906</json:string></issn><issue>12</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2083</json:string></eissn><title>Human Molecular Genetics</title></host><categories><wos><json:string>science</json:string><json:string>genetics & heredity</json:string><json:string>biochemistry & molecular biology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>biomedical research</json:string><json:string>genetics & heredity</json:string></scienceMetrix></categories><publicationDate>1997</publicationDate><copyrightDate>1997</copyrightDate><doi><json:string>10.1093/hmg/6.12.2091</json:string></doi><id>8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889</id><score>0.23354757</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Recurrent Mutations in a Single Exon Encoding the Evolutionarily Conserved Olfactomedin-Homology Domain of TIGR in Familial Open-Angle Glaucoma</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>© 1997 Oxford University Press</p></availability><date>1997</date></publicationStmt><notesStmt><note>These authors have contributed equally to this work</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Recurrent Mutations in a Single Exon Encoding the Evolutionarily Conserved Olfactomedin-Homology Domain of TIGR in Familial Open-Angle Glaucoma</title><author xml:id="author-1"><persName><forename type="first">Marie F.</forename><surname>Adam</surname></persName><note type="biography">+These authors have contributed equally to this work</note><affiliation>+These authors have contributed equally to this work</affiliation><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation></author><author xml:id="author-2"><persName><forename type="first">Ahmed</forename><surname>Belmouden</surname></persName><note type="biography">+These authors have contributed equally to this work</note><affiliation>+These authors have contributed equally to this work</affiliation><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation></author><author xml:id="author-3"><persName><forename type="first">Philippe</forename><surname>Binisti</surname></persName><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation></author><author xml:id="author-4"><persName><forename type="first">Antoine P.</forename><surname>Brézin</surname></persName><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation></author><author xml:id="author-5"><persName><forename type="first">Françoise</forename><surname>Valtot</surname></persName><affiliation>Institut du Glaucome, Hopital Saint-Joseph, Paris, France</affiliation></author><author xml:id="author-6"><persName><forename type="first">Alain</forename><surname>Béchetoille</surname></persName><affiliation>Service d'Ophtalmologie, C.H.U. Angers, Angers, France</affiliation></author><author xml:id="author-7"><persName><forename type="first">Jean-Claude</forename><surname>Dascotte</surname></persName><affiliation>Service d'Ophtalmologie, C.H.U. Lille, Lille, France</affiliation></author><author xml:id="author-8"><persName><forename type="first">Bruno</forename><surname>Copin</surname></persName><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation></author><author xml:id="author-9"><persName><forename type="first">Lucienne</forename><surname>Gomez</surname></persName><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation></author><author xml:id="author-10"><persName><forename type="first">André</forename><surname>Chaventré</surname></persName><affiliation>Laboratoire d'Anthropologie et de Démographie Génétiques, Université Bordeaux 2, Bordeaux, France</affiliation></author><author xml:id="author-11"><persName><forename type="first">Jean-François</forename><surname>Bach</surname></persName><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation></author><author xml:id="author-12" corresp="yes"><persName><forename type="first">Henri-Jean</forename><surname>Garchon</surname></persName><email>garchon@necker.fr</email><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation></author></analytic><monogr><title level="j">Human Molecular Genetics</title><title level="j" type="abbrev">Human Molecular Genetics</title><idno type="pISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="1997-11"></date><biblScope unit="volume">6</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="2091">2091</biblScope><biblScope unit="page" to="2097">2097</biblScope></imprint></monogr><idno type="istex">8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889</idno><idno type="DOI">10.1093/hmg/6.12.2091</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1997</date></creation><abstract><p>Primary open-angle glaucoma (POAG) is a highly prevalent cause of irreversible blindness which associates cupping of the optic disc and alteration of the visual field, elevation of intraocular pressure being a major risk factor. Provided diagnosis is made at an early stage, treatments are available to prevent visual impairment. A locus, GLC1A, has been mapped on chromosome 1q23ȓq25 in several families affected with juvenile-onset POAG (JOAG) and also in some families affected with juvenile and middle-age onset POAG. Recently, three mutations of the TIGR (Trabecular meshwork-Induced Glucocorticoid Response) gene were shown to be responsible for the disease in several American families and in unrelated POAG patients. We now describe five new mutations in eight French families. All mutations known to date appear to concentrate in the evolutionarily conserved C-terminal domain of TIGR which bears homology to frog olfactomedin, an extracellular matrix glycoprotein of the olfactory epithelium, to rat and human neuronal olfactomedin-related proteins and to F11C3.2, a protein from Caenorhabditis elegans. Moreover, this conserved domain of TIGR is encoded by a single exon to which mutation screening could be limited. Surprisingly, the TIGR message, which is abundantly transcribed in the trabecular meshwork and also in the ciliary body and the sclera, is not expressed in the optic nerve whose degeneration is, however, the primary lesion of POAG.</p></abstract></profileDesc><revisionDesc><change when="1997-11">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">hmg</journal-id><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-title>Human Molecular Genetics</journal-title><abbrev-journal-title>Human Molecular Genetics</abbrev-journal-title><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/hmg/6.12.2091</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Recurrent Mutations in a Single Exon Encoding the Evolutionarily Conserved Olfactomedin-Homology Domain of TIGR in Familial Open-Angle Glaucoma</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Adam</surname><given-names>Marie F.</given-names></name><xref rid="aff1" ref-type="aff"><sup>1,</sup></xref><xref rid="fn1" ref-type="fn"><sup>+</sup></xref></contrib><contrib contrib-type="author"><name><surname>Belmouden</surname><given-names>Ahmed</given-names></name><xref rid="aff1" ref-type="aff"><sup>1,</sup></xref><xref rid="fn1" ref-type="fn"><sup>+</sup></xref></contrib><contrib contrib-type="author"><name><surname>Binisti</surname><given-names>Philippe</given-names></name><xref rid="aff1" ref-type="aff"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Brézin</surname><given-names>Antoine P.</given-names></name><xref rid="aff1" ref-type="aff"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Valtot</surname><given-names>Françoise</given-names></name><xref rid="aff2" ref-type="aff"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Béchetoille</surname><given-names>Alain</given-names></name><xref rid="aff3" ref-type="aff"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dascotte</surname><given-names>Jean-Claude</given-names></name><xref rid="aff4" ref-type="aff"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Copin</surname><given-names>Bruno</given-names></name><xref rid="aff1" ref-type="aff"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gomez</surname><given-names>Lucienne</given-names></name><xref rid="aff1" ref-type="aff"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chaventré</surname><given-names>André</given-names></name><xref rid="aff5" ref-type="aff"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bach</surname><given-names>Jean-François</given-names></name><xref rid="aff1" ref-type="aff"><sup>1</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Garchon</surname><given-names>Henri-Jean</given-names></name><xref rid="aff1" ref-type="aff"><sup>1</sup></xref><xref rid="COR1" ref-type="corresp">*</xref></contrib><aff id="aff1"><label><sup>1</sup></label><institution>INSERM U25, Hôpital Necker</institution>, <addr-line>161 rue de Sèvres, 75743 Paris cedex 15, France</addr-line></aff><aff id="aff2"><label><sup>2</sup></label><institution>Institut du Glaucome, Hopital Saint-Joseph</institution>, <addr-line>Paris, France</addr-line></aff><aff id="aff3"><label><sup>3</sup></label><institution>Service d'Ophtalmologie</institution>, <addr-line>C.H.U. Angers, Angers, France</addr-line></aff><aff id="aff4"><label><sup>4</sup></label><institution>Service d'Ophtalmologie</institution>, <addr-line>C.H.U. Lille, Lille, France</addr-line></aff><aff id="aff5"><label><sup>5</sup></label><institution>Laboratoire d'Anthropologie et de Démographie Génétiques, Université Bordeaux 2</institution>, <addr-line>Bordeaux, France</addr-line></aff></contrib-group><author-notes><corresp id="COR1"><label>*</label>To whom correspondence should be addressed. Tel: +33 1 44 49 53 67; Fax: +33 1 43 06 23 88; Email: <email>garchon@necker.fr</email></corresp><fn fn-type="equal" id="fn1"><label><sup>+</sup></label><p>These authors have contributed equally to this work</p></fn></author-notes><pub-date pub-type="ppub"><month>11</month><year>1997</year></pub-date><volume>6</volume><issue>12</issue><fpage>2091</fpage><lpage>2097</lpage><history><date date-type="received"><day>26</day><month>6</month><year>1997</year></date><date date-type="accepted"><day>13</day><month>8</month><year>1997</year></date></history><copyright-statement>© 1997 Oxford University Press</copyright-statement><copyright-year>1997</copyright-year><abstract><p>Primary open-angle glaucoma (POAG) is a highly prevalent cause of irreversible blindness which associates cupping of the optic disc and alteration of the visual field, elevation of intraocular pressure being a major risk factor. Provided diagnosis is made at an early stage, treatments are available to prevent visual impairment. A locus, GLC1A, has been mapped on chromosome 1q23ȓq25 in several families affected with juvenile-onset POAG (JOAG) and also in some families affected with juvenile and middle-age onset POAG. Recently, three mutations of the TIGR (Trabecular meshwork-Induced Glucocorticoid Response) gene were shown to be responsible for the disease in several American families and in unrelated POAG patients. We now describe five new mutations in eight French families. All mutations known to date appear to concentrate in the evolutionarily conserved C-terminal domain of TIGR which bears homology to frog olfactomedin, an extracellular matrix glycoprotein of the olfactory epithelium, to rat and human neuronal olfactomedin-related proteins and to F11C3.2, a protein from <italic>Caenorhabditis elegans</italic>. Moreover, this conserved domain of TIGR is encoded by a single exon to which mutation screening could be limited. Surprisingly, the TIGR message, which is abundantly transcribed in the trabecular meshwork and also in the ciliary body and the sclera, is not expressed in the optic nerve whose degeneration is, however, the primary lesion of POAG.</p></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Recurrent Mutations in a Single Exon Encoding the Evolutionarily Conserved Olfactomedin-Homology Domain of TIGR in Familial Open-Angle Glaucoma</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Recurrent Mutations in a Single Exon Encoding the Evolutionarily Conserved Olfactomedin-Homology Domain of TIGR in Familial Open-Angle Glaucoma</title></titleInfo><name type="personal"><namePart type="given">Marie F.</namePart><namePart type="family">Adam</namePart><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation><description>+These authors have contributed equally to this work</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ahmed</namePart><namePart type="family">Belmouden</namePart><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation><description>+These authors have contributed equally to this work</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Philippe</namePart><namePart type="family">Binisti</namePart><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Antoine P.</namePart><namePart type="family">Brézin</namePart><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Françoise</namePart><namePart type="family">Valtot</namePart><affiliation>Institut du Glaucome, Hopital Saint-Joseph, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alain</namePart><namePart type="family">Béchetoille</namePart><affiliation>Service d'Ophtalmologie, C.H.U. Angers, Angers, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean-Claude</namePart><namePart type="family">Dascotte</namePart><affiliation>Service d'Ophtalmologie, C.H.U. Lille, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bruno</namePart><namePart type="family">Copin</namePart><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lucienne</namePart><namePart type="family">Gomez</namePart><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">André</namePart><namePart type="family">Chaventré</namePart><affiliation>Laboratoire d'Anthropologie et de Démographie Génétiques, Université Bordeaux 2, Bordeaux, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean-François</namePart><namePart type="family">Bach</namePart><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Henri-Jean</namePart><namePart type="family">Garchon</namePart><affiliation>INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France</affiliation><affiliation>E-mail: garchon@necker.fr</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">1997-11</dateIssued><copyrightDate encoding="w3cdtf">1997</copyrightDate></originInfo><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Primary open-angle glaucoma (POAG) is a highly prevalent cause of irreversible blindness which associates cupping of the optic disc and alteration of the visual field, elevation of intraocular pressure being a major risk factor. Provided diagnosis is made at an early stage, treatments are available to prevent visual impairment. A locus, GLC1A, has been mapped on chromosome 1q23ȓq25 in several families affected with juvenile-onset POAG (JOAG) and also in some families affected with juvenile and middle-age onset POAG. Recently, three mutations of the TIGR (Trabecular meshwork-Induced Glucocorticoid Response) gene were shown to be responsible for the disease in several American families and in unrelated POAG patients. We now describe five new mutations in eight French families. All mutations known to date appear to concentrate in the evolutionarily conserved C-terminal domain of TIGR which bears homology to frog olfactomedin, an extracellular matrix glycoprotein of the olfactory epithelium, to rat and human neuronal olfactomedin-related proteins and to F11C3.2, a protein from Caenorhabditis elegans. Moreover, this conserved domain of TIGR is encoded by a single exon to which mutation screening could be limited. Surprisingly, the TIGR message, which is abundantly transcribed in the trabecular meshwork and also in the ciliary body and the sclera, is not expressed in the optic nerve whose degeneration is, however, the primary lesion of POAG.</abstract><note type="footnotes">These authors have contributed equally to this work</note><relatedItem type="host"><titleInfo><title>Human Molecular Genetics</title></titleInfo><titleInfo type="abbreviated"><title>Human Molecular Genetics</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0964-6906</identifier><identifier type="eISSN">1460-2083</identifier><identifier type="PublisherID">hmg</identifier><identifier type="PublisherID-hwp">hmg</identifier><part><date>1997</date><detail type="volume"><caption>vol.</caption><number>6</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>2091</start><end>2097</end></extent></part></relatedItem><identifier type="istex">8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889</identifier><identifier type="DOI">10.1093/hmg/6.12.2091</identifier><accessCondition type="use and reproduction" contentType="copyright">© 1997 Oxford University Press</accessCondition><recordInfo><recordContentSource>OUP</recordContentSource></recordInfo></mods></metadata><annexes><json:item><extension>jpeg</extension><original>true</original><mimetype>image/jpeg</mimetype><uri>https://api.istex.fr/document/8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889/annexes/jpeg</uri></json:item><json:item><extension>gif</extension><original>true</original><mimetype>image/gif</mimetype><uri>https://api.istex.fr/document/8DD2A0B23C32C2D972C04A58BA8F6E0AB2BB3889/annexes/gif</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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