CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma
Introduction: Primary open-angle glaucoma (POAG) is a leading cause of visual impairment worldwide and a complex genetic disorder that affects mostly adults. Mutations in the MYOCILIN (MYOC) and OPTINEURIN genes account for rare forms with a Mendelian inheritance and for
Gespeichert in:
| Veröffentlicht in: | Journal of medical genetics 2004-09, Vol.41 (9), p.647-651 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 651 |
|---|---|
| container_issue | 9 |
| container_start_page | 647 |
| container_title | Journal of medical genetics |
| container_volume | 41 |
| creator | Melki, R Colomb, E Lefort, N Brézin, A P Garchon, H-J |
| description | Introduction: Primary open-angle glaucoma (POAG) is a leading cause of visual impairment worldwide and a complex genetic disorder that affects mostly adults. Mutations in the MYOCILIN (MYOC) and OPTINEURIN genes account for rare forms with a Mendelian inheritance and for |
| doi_str_mv | 10.1136/jmg.2004.020024 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1735887</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>66840040</sourcerecordid><originalsourceid>FETCH-LOGICAL-b551t-ed8163085414eb8dead4b16b5f5415e065177d5c38dad725626ce608e1b7053d3</originalsourceid><addsrcrecordid>eNqFkc1v1DAQxS0EotuFMzdkCdEDUrae-HMvlWBF-VAFlSggTpaTzO5mSZzFToD-93iVqAUuvdjSm59nnucR8gTYAoCr0127WeSMiQVLZy7ukRkIZTKVC3GfzJKUZ7lc8iNyHOOOMeAa1ENyBJKLXC35jFyuvl3CK6Dt0Lu-7nyktafnAX25pfukoO8j_VX3W4ouNNdZIrCn-1C3LlzTbo8-c37TIN00bii71j0iD9auifh4uufk8_nrq9Xb7OLjm3erlxdZISX0GVYGFGdGChBYmApdJQpQhVwnRSJTErSuZMlN5SqdS5WrEhUzCIVmkld8Ts7GvvuhaLEqk9HgGjs5s52r7b8VX2_tpvtpQXNpjE4NTqYGofsxYOxtW8cSm8Z57IZolTIibZbdCYJJhliKY06e_QfuuiH4tIU01ABII8Ek6nSkytDFGHB94xmYPYRqU6j2EKodQ00vnv791Vt-SjEBzyfAxdI16-B8WcdbTgE7GEhcNnJ17PH3Td2F71ZprqX98GVl1SfB3rPlV3uV-BcjX7S7O13-AV2yxU4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1781158518</pqid></control><display><type>article</type><title>CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Melki, R ; Colomb, E ; Lefort, N ; Brézin, A P ; Garchon, H-J</creator><creatorcontrib>Melki, R ; Colomb, E ; Lefort, N ; Brézin, A P ; Garchon, H-J</creatorcontrib><description>Introduction: Primary open-angle glaucoma (POAG) is a leading cause of visual impairment worldwide and a complex genetic disorder that affects mostly adults. Mutations in the MYOCILIN (MYOC) and OPTINEURIN genes account for rare forms with a Mendelian inheritance and for <5% of all POAG cases. The CYP1B1 gene, a member of the cytochrome P450 gene family, is a major cause of primary congenital glaucoma (PCG), a rare and severely blinding disease with recessive inheritance. However, CYP1B1 mutations have also been associated with cases of juvenile-onset glaucoma in some PCG families or shown to modify the age of onset of glaucoma linked to a MYOC mutation in a large family. Objective: To investigate the role of CYP1B1 mutations in POAG predisposition, irrespective of the presence of a MYOC mutation. Methods and subjects:CYP1B1 coding region variation was characterised by denaturing high performance liquid chromatography (DHPLC) and sequencing in 236 unrelated French Caucasian POAG patients and 47 population-matched controls. Results: Eleven (4.6%) patients carried one or two mutated CYP1B1 gene(s) and no MYOC mutation. They showed juvenile or middle-age onset of disease (median age at diagnosis, 40 years, range 13–52), significantly earlier than in non-carrier patients. Apart from one, all mutations detected in POAG patients were previously associated with PCG. Conclusion:CYP1B1 mutations might pose a significant risk for early-onset POAG and might also modify glaucoma phenotype in patients who do not carry a MYOC mutation.</description><identifier>ISSN: 0022-2593</identifier><identifier>ISSN: 1468-6244</identifier><identifier>EISSN: 1468-6244</identifier><identifier>DOI: 10.1136/jmg.2004.020024</identifier><identifier>PMID: 15342693</identifier><identifier>CODEN: JMDGAE</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd</publisher><subject>Adolescent ; Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Aryl Hydrocarbon Hydroxylases - genetics ; Biological and medical sciences ; Child ; Chromatography ; Classical genetics, quantitative genetics, hybrids ; CYP1B1 ; Cytochrome P-450 CYP1B1 ; denaturing high performance liquid chromatography ; DHPLC ; dimethylsulfoxide ; DMSO ; DNA Mutational Analysis ; Female ; France ; Fundamental and applied biological sciences. Psychology ; Genetic Testing ; Genetic Variation - genetics ; genetics ; Genetics of eukaryotes. Biological and molecular evolution ; Glaucoma ; Glaucoma and intraocular pressure ; Glaucoma, Open-Angle - genetics ; Glaucoma, Open-Angle - physiopathology ; Human ; Humans ; intraocular pressure ; IOP ; Male ; Medical sciences ; Middle Aged ; Mutation ; Mutation - genetics ; Ophthalmology ; Original ; PCG ; Pedigree ; POAG ; primary congenital glaucoma ; primary open-angle glaucoma ; screening ; TEAA ; triethylammonium acetate</subject><ispartof>Journal of medical genetics, 2004-09, Vol.41 (9), p.647-651</ispartof><rights>Copyright 2004 Journal of Medical Genetics</rights><rights>2004 INIST-CNRS</rights><rights>Copyright: 2004 Copyright 2004 Journal of Medical Genetics</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b551t-ed8163085414eb8dead4b16b5f5415e065177d5c38dad725626ce608e1b7053d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1735887/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1735887/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16101781$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15342693$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Melki, R</creatorcontrib><creatorcontrib>Colomb, E</creatorcontrib><creatorcontrib>Lefort, N</creatorcontrib><creatorcontrib>Brézin, A P</creatorcontrib><creatorcontrib>Garchon, H-J</creatorcontrib><title>CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma</title><title>Journal of medical genetics</title><addtitle>J Med Genet</addtitle><description>Introduction: Primary open-angle glaucoma (POAG) is a leading cause of visual impairment worldwide and a complex genetic disorder that affects mostly adults. Mutations in the MYOCILIN (MYOC) and OPTINEURIN genes account for rare forms with a Mendelian inheritance and for <5% of all POAG cases. The CYP1B1 gene, a member of the cytochrome P450 gene family, is a major cause of primary congenital glaucoma (PCG), a rare and severely blinding disease with recessive inheritance. However, CYP1B1 mutations have also been associated with cases of juvenile-onset glaucoma in some PCG families or shown to modify the age of onset of glaucoma linked to a MYOC mutation in a large family. Objective: To investigate the role of CYP1B1 mutations in POAG predisposition, irrespective of the presence of a MYOC mutation. Methods and subjects:CYP1B1 coding region variation was characterised by denaturing high performance liquid chromatography (DHPLC) and sequencing in 236 unrelated French Caucasian POAG patients and 47 population-matched controls. Results: Eleven (4.6%) patients carried one or two mutated CYP1B1 gene(s) and no MYOC mutation. They showed juvenile or middle-age onset of disease (median age at diagnosis, 40 years, range 13–52), significantly earlier than in non-carrier patients. Apart from one, all mutations detected in POAG patients were previously associated with PCG. Conclusion:CYP1B1 mutations might pose a significant risk for early-onset POAG and might also modify glaucoma phenotype in patients who do not carry a MYOC mutation.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age of Onset</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Chromatography</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>CYP1B1</subject><subject>Cytochrome P-450 CYP1B1</subject><subject>denaturing high performance liquid chromatography</subject><subject>DHPLC</subject><subject>dimethylsulfoxide</subject><subject>DMSO</subject><subject>DNA Mutational Analysis</subject><subject>Female</subject><subject>France</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic Testing</subject><subject>Genetic Variation - genetics</subject><subject>genetics</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Glaucoma</subject><subject>Glaucoma and intraocular pressure</subject><subject>Glaucoma, Open-Angle - genetics</subject><subject>Glaucoma, Open-Angle - physiopathology</subject><subject>Human</subject><subject>Humans</subject><subject>intraocular pressure</subject><subject>IOP</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Ophthalmology</subject><subject>Original</subject><subject>PCG</subject><subject>Pedigree</subject><subject>POAG</subject><subject>primary congenital glaucoma</subject><subject>primary open-angle glaucoma</subject><subject>screening</subject><subject>TEAA</subject><subject>triethylammonium acetate</subject><issn>0022-2593</issn><issn>1468-6244</issn><issn>1468-6244</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc1v1DAQxS0EotuFMzdkCdEDUrae-HMvlWBF-VAFlSggTpaTzO5mSZzFToD-93iVqAUuvdjSm59nnucR8gTYAoCr0127WeSMiQVLZy7ukRkIZTKVC3GfzJKUZ7lc8iNyHOOOMeAa1ENyBJKLXC35jFyuvl3CK6Dt0Lu-7nyktafnAX25pfukoO8j_VX3W4ouNNdZIrCn-1C3LlzTbo8-c37TIN00bii71j0iD9auifh4uufk8_nrq9Xb7OLjm3erlxdZISX0GVYGFGdGChBYmApdJQpQhVwnRSJTErSuZMlN5SqdS5WrEhUzCIVmkld8Ts7GvvuhaLEqk9HgGjs5s52r7b8VX2_tpvtpQXNpjE4NTqYGofsxYOxtW8cSm8Z57IZolTIibZbdCYJJhliKY06e_QfuuiH4tIU01ABII8Ek6nSkytDFGHB94xmYPYRqU6j2EKodQ00vnv791Vt-SjEBzyfAxdI16-B8WcdbTgE7GEhcNnJ17PH3Td2F71ZprqX98GVl1SfB3rPlV3uV-BcjX7S7O13-AV2yxU4</recordid><startdate>20040901</startdate><enddate>20040901</enddate><creator>Melki, R</creator><creator>Colomb, E</creator><creator>Lefort, N</creator><creator>Brézin, A P</creator><creator>Garchon, H-J</creator><general>BMJ Publishing Group Ltd</general><general>BMJ</general><general>BMJ Publishing Group LTD</general><general>BMJ Group</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040901</creationdate><title>CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma</title><author>Melki, R ; Colomb, E ; Lefort, N ; Brézin, A P ; Garchon, H-J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b551t-ed8163085414eb8dead4b16b5f5415e065177d5c38dad725626ce608e1b7053d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age of Onset</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aryl Hydrocarbon Hydroxylases - genetics</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Chromatography</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>CYP1B1</topic><topic>Cytochrome P-450 CYP1B1</topic><topic>denaturing high performance liquid chromatography</topic><topic>DHPLC</topic><topic>dimethylsulfoxide</topic><topic>DMSO</topic><topic>DNA Mutational Analysis</topic><topic>Female</topic><topic>France</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic Testing</topic><topic>Genetic Variation - genetics</topic><topic>genetics</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Glaucoma</topic><topic>Glaucoma and intraocular pressure</topic><topic>Glaucoma, Open-Angle - genetics</topic><topic>Glaucoma, Open-Angle - physiopathology</topic><topic>Human</topic><topic>Humans</topic><topic>intraocular pressure</topic><topic>IOP</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Ophthalmology</topic><topic>Original</topic><topic>PCG</topic><topic>Pedigree</topic><topic>POAG</topic><topic>primary congenital glaucoma</topic><topic>primary open-angle glaucoma</topic><topic>screening</topic><topic>TEAA</topic><topic>triethylammonium acetate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Melki, R</creatorcontrib><creatorcontrib>Colomb, E</creatorcontrib><creatorcontrib>Lefort, N</creatorcontrib><creatorcontrib>Brézin, A P</creatorcontrib><creatorcontrib>Garchon, H-J</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of medical genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Melki, R</au><au>Colomb, E</au><au>Lefort, N</au><au>Brézin, A P</au><au>Garchon, H-J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma</atitle><jtitle>Journal of medical genetics</jtitle><addtitle>J Med Genet</addtitle><date>2004-09-01</date><risdate>2004</risdate><volume>41</volume><issue>9</issue><spage>647</spage><epage>651</epage><pages>647-651</pages><issn>0022-2593</issn><issn>1468-6244</issn><eissn>1468-6244</eissn><coden>JMDGAE</coden><abstract>Introduction: Primary open-angle glaucoma (POAG) is a leading cause of visual impairment worldwide and a complex genetic disorder that affects mostly adults. Mutations in the MYOCILIN (MYOC) and OPTINEURIN genes account for rare forms with a Mendelian inheritance and for <5% of all POAG cases. The CYP1B1 gene, a member of the cytochrome P450 gene family, is a major cause of primary congenital glaucoma (PCG), a rare and severely blinding disease with recessive inheritance. However, CYP1B1 mutations have also been associated with cases of juvenile-onset glaucoma in some PCG families or shown to modify the age of onset of glaucoma linked to a MYOC mutation in a large family. Objective: To investigate the role of CYP1B1 mutations in POAG predisposition, irrespective of the presence of a MYOC mutation. Methods and subjects:CYP1B1 coding region variation was characterised by denaturing high performance liquid chromatography (DHPLC) and sequencing in 236 unrelated French Caucasian POAG patients and 47 population-matched controls. Results: Eleven (4.6%) patients carried one or two mutated CYP1B1 gene(s) and no MYOC mutation. They showed juvenile or middle-age onset of disease (median age at diagnosis, 40 years, range 13–52), significantly earlier than in non-carrier patients. Apart from one, all mutations detected in POAG patients were previously associated with PCG. Conclusion:CYP1B1 mutations might pose a significant risk for early-onset POAG and might also modify glaucoma phenotype in patients who do not carry a MYOC mutation.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd</pub><pmid>15342693</pmid><doi>10.1136/jmg.2004.020024</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2593 |
| ispartof | Journal of medical genetics, 2004-09, Vol.41 (9), p.647-651 |
| issn | 0022-2593 1468-6244 1468-6244 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1735887 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Adolescent Adult Age of Onset Aged Aged, 80 and over Aryl Hydrocarbon Hydroxylases - genetics Biological and medical sciences Child Chromatography Classical genetics, quantitative genetics, hybrids CYP1B1 Cytochrome P-450 CYP1B1 denaturing high performance liquid chromatography DHPLC dimethylsulfoxide DMSO DNA Mutational Analysis Female France Fundamental and applied biological sciences. Psychology Genetic Testing Genetic Variation - genetics genetics Genetics of eukaryotes. Biological and molecular evolution Glaucoma Glaucoma and intraocular pressure Glaucoma, Open-Angle - genetics Glaucoma, Open-Angle - physiopathology Human Humans intraocular pressure IOP Male Medical sciences Middle Aged Mutation Mutation - genetics Ophthalmology Original PCG Pedigree POAG primary congenital glaucoma primary open-angle glaucoma screening TEAA triethylammonium acetate |
| title | CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T14%3A54%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CYP1B1%20mutations%20in%20French%20patients%20with%20early-onset%20primary%20open-angle%20glaucoma&rft.jtitle=Journal%20of%20medical%20genetics&rft.au=Melki,%20R&rft.date=2004-09-01&rft.volume=41&rft.issue=9&rft.spage=647&rft.epage=651&rft.pages=647-651&rft.issn=0022-2593&rft.eissn=1468-6244&rft.coden=JMDGAE&rft_id=info:doi/10.1136/jmg.2004.020024&rft_dat=%3Cproquest_pubme%3E66840040%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1781158518&rft_id=info:pmid/15342693&rfr_iscdi=true |