Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson’s disease
Identifieur interne : 001321 ( Main/Corpus ); précédent : 001320; suivant : 001322Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson’s disease
Auteurs : S. Lesage ; C. Condroyer ; A. Lannuzel ; E. Lohmann ; A. Troiano ; F. Tison ; P. Damier ; S. Thobois ; A-M Ouvrard-Hernandez ; S. Rivaud-Péchoux ; C. Brefel-Courbon ; A. Destée ; C. Tranchant ; M. Romana ; L. Leclere ; A. Dürr ; A. BriceSource :
- Journal of Medical Genetics [ 0022-2593 ] ; 2009-07.
Abstract
Background: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson’s disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. Methods: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson’s disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). Results: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. Conclusion: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson’s disease in Europe and North Africa.
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DOI: 10.1136/jmg.2008.062612
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Rivaud-Péchoux</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Brefel Courbon, C" sort="Brefel Courbon, C" uniqKey="Brefel Courbon C" first="C" last="Brefel-Courbon">C. Brefel-Courbon</name><affiliation><mods:affiliation>Centre d’Investigation Clinique, Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, CHU Toulouse, Toulouse, France</mods:affiliation></affiliation></author><author><name sortKey="Destee, A" sort="Destee, A" uniqKey="Destee A" first="A" last="Destée">A. Destée</name><affiliation><mods:affiliation>EA2683, Service de Neurologie, Hôpital R. Salengro, CHRU de Lille, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Tranchant, C" sort="Tranchant, C" uniqKey="Tranchant C" first="C" last="Tranchant">C. Tranchant</name><affiliation><mods:affiliation>Pôle Tête-Cou-CETD, Service de Neurologie, Hôpitaux Universitaires, Strasbourg, France</mods:affiliation></affiliation></author><author><name sortKey="Romana, M" sort="Romana, M" uniqKey="Romana M" first="M" last="Romana">M. Romana</name><affiliation><mods:affiliation>INSERM, U763, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</mods:affiliation></affiliation></author><author><name sortKey="Leclere, L" sort="Leclere, L" uniqKey="Leclere L" first="L" last="Leclere">L. Leclere</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Durr, A" sort="Durr, A" uniqKey="Durr A" first="A" last="Dürr">A. Dürr</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Brice, A" sort="Brice, A" uniqKey="Brice A" first="A" last="Brice">A. Brice</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:D85D9436A64FCD3297283BD8AE39631C9AFCE5B4</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1136/jmg.2008.062612</idno><idno type="url">https://api.istex.fr/document/D85D9436A64FCD3297283BD8AE39631C9AFCE5B4/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001321</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson’s disease</title><author><name sortKey="Lesage, S" sort="Lesage, S" uniqKey="Lesage S" first="S" last="Lesage">S. Lesage</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Condroyer, C" sort="Condroyer, C" uniqKey="Condroyer C" first="C" last="Condroyer">C. Condroyer</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Lannuzel, A" sort="Lannuzel, A" uniqKey="Lannuzel A" first="A" last="Lannuzel">A. Lannuzel</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Service de Neurologie, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</mods:affiliation></affiliation></author><author><name sortKey="Lohmann, E" sort="Lohmann, E" uniqKey="Lohmann E" first="E" last="Lohmann">E. Lohmann</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Troiano, A" sort="Troiano, A" uniqKey="Troiano A" first="A" last="Troiano">A. Troiano</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Tison, F" sort="Tison, F" uniqKey="Tison F" first="F" last="Tison">F. Tison</name><affiliation><mods:affiliation>Service de Neurologie, Hôpital Haut-Lévêque, Pessac, France</mods:affiliation></affiliation></author><author><name sortKey="Damier, P" sort="Damier, P" uniqKey="Damier P" first="P" last="Damier">P. Damier</name><affiliation><mods:affiliation>CHU Nantes, CIC0004, Service de Neurologie, Nantes, France</mods:affiliation></affiliation></author><author><name sortKey="Thobois, S" sort="Thobois, S" uniqKey="Thobois S" first="S" last="Thobois">S. Thobois</name><affiliation><mods:affiliation>Unité 401, Pôle des Spécialités Neurologiques, Hôpital Neurologique Pierre Wertheimer, Bron, France</mods:affiliation></affiliation></author><author><name sortKey="Ouvrard Hernandez, A M" sort="Ouvrard Hernandez, A M" uniqKey="Ouvrard Hernandez A" first="A-M" last="Ouvrard-Hernandez">A-M Ouvrard-Hernandez</name><affiliation><mods:affiliation>Département de Neurologie, CHU de Grenoble, Grenoble, France</mods:affiliation></affiliation></author><author><name sortKey="Rivaud Pechoux, S" sort="Rivaud Pechoux, S" uniqKey="Rivaud Pechoux S" first="S" last="Rivaud-Péchoux">S. Rivaud-Péchoux</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Brefel Courbon, C" sort="Brefel Courbon, C" uniqKey="Brefel Courbon C" first="C" last="Brefel-Courbon">C. Brefel-Courbon</name><affiliation><mods:affiliation>Centre d’Investigation Clinique, Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, CHU Toulouse, Toulouse, France</mods:affiliation></affiliation></author><author><name sortKey="Destee, A" sort="Destee, A" uniqKey="Destee A" first="A" last="Destée">A. Destée</name><affiliation><mods:affiliation>EA2683, Service de Neurologie, Hôpital R. Salengro, CHRU de Lille, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Tranchant, C" sort="Tranchant, C" uniqKey="Tranchant C" first="C" last="Tranchant">C. Tranchant</name><affiliation><mods:affiliation>Pôle Tête-Cou-CETD, Service de Neurologie, Hôpitaux Universitaires, Strasbourg, France</mods:affiliation></affiliation></author><author><name sortKey="Romana, M" sort="Romana, M" uniqKey="Romana M" first="M" last="Romana">M. Romana</name><affiliation><mods:affiliation>INSERM, U763, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</mods:affiliation></affiliation></author><author><name sortKey="Leclere, L" sort="Leclere, L" uniqKey="Leclere L" first="L" last="Leclere">L. Leclere</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Durr, A" sort="Durr, A" uniqKey="Durr A" first="A" last="Dürr">A. Dürr</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Brice, A" sort="Brice, A" uniqKey="Brice A" first="A" last="Brice">A. Brice</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="ISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2009-07">2009-07</date><biblScope unit="volume">46</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="458">458</biblScope></imprint><idno type="ISSN">0022-2593</idno></series><idno type="istex">D85D9436A64FCD3297283BD8AE39631C9AFCE5B4</idno><idno type="DOI">10.1136/jmg.2008.062612</idno><idno type="href">jmedgenet-46-458.pdf</idno><idno type="ArticleID">mg62612</idno><idno type="PMID">19357115</idno><idno type="local">jmedgenet;46/7/458</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Background: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson’s disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. Methods: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson’s disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). Results: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. Conclusion: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson’s disease in Europe and North Africa.</div></front></TEI><istex><corpusName>bmj</corpusName><author><json:item><name>S Lesage</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string><json:string>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</json:string></affiliations></json:item><json:item><name>C Condroyer</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string><json:string>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</json:string></affiliations></json:item><json:item><name>A Lannuzel</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string><json:string>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</json:string><json:string>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</json:string><json:string>Service de Neurologie, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</json:string></affiliations></json:item><json:item><name>E Lohmann</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string><json:string>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</json:string><json:string>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</json:string></affiliations></json:item><json:item><name>A Troiano</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string><json:string>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</json:string></affiliations></json:item><json:item><name>F Tison</name><affiliations><json:string>Service de Neurologie, Hôpital Haut-Lévêque, Pessac, France</json:string></affiliations></json:item><json:item><name>P Damier</name><affiliations><json:string>CHU Nantes, CIC0004, Service de Neurologie, Nantes, France</json:string></affiliations></json:item><json:item><name>S Thobois</name><affiliations><json:string>Unité 401, Pôle des Spécialités Neurologiques, Hôpital Neurologique Pierre Wertheimer, Bron, France</json:string></affiliations></json:item><json:item><name>A-M Ouvrard-Hernandez</name><affiliations><json:string>Département de Neurologie, CHU de Grenoble, Grenoble, France</json:string></affiliations></json:item><json:item><name>S Rivaud-Péchoux</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string><json:string>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</json:string></affiliations></json:item><json:item><name>C Brefel-Courbon</name><affiliations><json:string>Centre d’Investigation Clinique, Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, CHU Toulouse, Toulouse, France</json:string></affiliations></json:item><json:item><name>A Destée</name><affiliations><json:string>EA2683, Service de Neurologie, Hôpital R. Salengro, CHRU de Lille, Lille, France</json:string></affiliations></json:item><json:item><name>C Tranchant</name><affiliations><json:string>Pôle Tête-Cou-CETD, Service de Neurologie, Hôpitaux Universitaires, Strasbourg, France</json:string></affiliations></json:item><json:item><name>M Romana</name><affiliations><json:string>INSERM, U763, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</json:string></affiliations></json:item><json:item><name>L Leclere</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string><json:string>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</json:string></affiliations></json:item><json:item><name>A Dürr</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string><json:string>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</json:string><json:string>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</json:string><json:string>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</json:string></affiliations></json:item><json:item><name>A Brice</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string><json:string>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</json:string><json:string>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</json:string><json:string>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Letters to JMG</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Genetic screening / counselling</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Background: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson’s disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. Methods: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson’s disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). Results: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. Conclusion: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson’s disease in Europe and North Africa.</abstract><qualityIndicators><score>7.676</score><pdfVersion>1.2</pdfVersion><pdfPageSize>595.276 x 793.701 pts</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>2</keywordCount><abstractCharCount>1487</abstractCharCount><pdfWordCount>5233</pdfWordCount><pdfCharCount>34739</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>223</abstractWordCount></qualityIndicators><title>Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson’s disease</title><pmid><json:string>19357115</json:string></pmid><corporate><json:item><name>for the French Parkinson’s Disease Genetics Study Group*</name></json:item></corporate><genre><json:string>research-article</json:string></genre><host><volume>46</volume><pages><first>458</first></pages><issn><json:string>0022-2593</json:string></issn><issue>7</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1468-6244</json:string></eissn><title>Journal of Medical Genetics</title></host><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1136/jmg.2008.062612</json:string></doi><id>D85D9436A64FCD3297283BD8AE39631C9AFCE5B4</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/D85D9436A64FCD3297283BD8AE39631C9AFCE5B4/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/D85D9436A64FCD3297283BD8AE39631C9AFCE5B4/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/D85D9436A64FCD3297283BD8AE39631C9AFCE5B4/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson’s disease</title><respStmt xml:id="ISTEX-API" resp="Références bibliographiques récupérées via GROBID" name="ISTEX-API (INIST-CNRS)"></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>BMJ Publishing Group Ltd</publisher><availability><p>BMJ</p></availability><date>2009-04-08</date></publicationStmt><notesStmt><note>Additional tables and figure are published online only at http://jmg.bmj.com/content/vol46/issue7</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson’s disease</title><author><orgName>for the French Parkinson’s Disease Genetics Study Group*</orgName></author><author><persName><forename type="first">S</forename><surname>Lesage</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation></author><author><persName><forename type="first">C</forename><surname>Condroyer</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation></author><author><persName><forename type="first">A</forename><surname>Lannuzel</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</affiliation><affiliation>Service de Neurologie, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</affiliation></author><author><persName><forename type="first">E</forename><surname>Lohmann</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</affiliation></author><author><persName><forename type="first">A</forename><surname>Troiano</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation></author><author><persName><forename type="first">F</forename><surname>Tison</surname></persName><affiliation>Service de Neurologie, Hôpital Haut-Lévêque, Pessac, France</affiliation></author><author><persName><forename type="first">P</forename><surname>Damier</surname></persName><affiliation>CHU Nantes, CIC0004, Service de Neurologie, Nantes, France</affiliation></author><author><persName><forename type="first">S</forename><surname>Thobois</surname></persName><affiliation>Unité 401, Pôle des Spécialités Neurologiques, Hôpital Neurologique Pierre Wertheimer, Bron, France</affiliation></author><author><persName><forename type="first">A-M</forename><surname>Ouvrard-Hernandez</surname></persName><affiliation>Département de Neurologie, CHU de Grenoble, Grenoble, France</affiliation></author><author><persName><forename type="first">S</forename><surname>Rivaud-Péchoux</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation></author><author><persName><forename type="first">C</forename><surname>Brefel-Courbon</surname></persName><affiliation>Centre d’Investigation Clinique, Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, CHU Toulouse, Toulouse, France</affiliation></author><author><persName><forename type="first">A</forename><surname>Destée</surname></persName><affiliation>EA2683, Service de Neurologie, Hôpital R. Salengro, CHRU de Lille, Lille, France</affiliation></author><author><persName><forename type="first">C</forename><surname>Tranchant</surname></persName><affiliation>Pôle Tête-Cou-CETD, Service de Neurologie, Hôpitaux Universitaires, Strasbourg, France</affiliation></author><author><persName><forename type="first">M</forename><surname>Romana</surname></persName><affiliation>INSERM, U763, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</affiliation></author><author><persName><forename type="first">L</forename><surname>Leclere</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation></author><author><persName><forename type="first">A</forename><surname>Dürr</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</affiliation></author><author><persName><forename type="first">A</forename><surname>Brice</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</affiliation></author></analytic><monogr><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="pISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2009-07"></date><biblScope unit="volume">46</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="458">458</biblScope></imprint></monogr><idno type="istex">D85D9436A64FCD3297283BD8AE39631C9AFCE5B4</idno><idno type="DOI">10.1136/jmg.2008.062612</idno><idno type="href">jmedgenet-46-458.pdf</idno><idno type="ArticleID">mg62612</idno><idno type="PMID">19357115</idno><idno type="local">jmedgenet;46/7/458</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009-04-08</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Background: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson’s disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. Methods: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson’s disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). Results: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. Conclusion: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson’s disease in Europe and North Africa.</p></abstract><textClass><keywords scheme="keyword"><list><head>hwp-journal-coll</head><item><term>Genetic screening / counselling</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-04-08">Created</change><change when="2009-07">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-3-14">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/D85D9436A64FCD3297283BD8AE39631C9AFCE5B4/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus bmj" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="no"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal 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pub-id-type="pmid">19357115</article-id><article-id pub-id-type="other">458</article-id><article-id pub-id-type="other">jmg.2008.062612</article-id><article-categories><subj-group subj-group-type="heading"><subject>Letters to JMG</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Genetic screening / counselling</subject></subj-group></article-categories><title-group><article-title>Molecular analyses of the <italic>LRRK2</italic> gene in European and North African autosomal dominant Parkinson’s disease</article-title><alt-title alt-title-type="running-head">Letter to JMG</alt-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Lesage</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Condroyer</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Lannuzel</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Lohmann</surname><given-names>E</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Troiano</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Tison</surname><given-names>F</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Damier</surname><given-names>P</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Thobois</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ouvrard-Hernandez</surname><given-names>A-M</given-names></name><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Rivaud-Péchoux</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Brefel-Courbon</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Destée</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Tranchant</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff11">11</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Romana</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff12">12</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Leclere</surname><given-names>L</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Dürr</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff13">13</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Brice</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff13">13</xref></contrib><contrib contrib-type="author" xlink:type="simple"><collab xlink:type="simple">for the French Parkinson’s Disease Genetics Study Group<sup>*</sup></collab></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>INSERM, UMR_S679, Paris, France</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</addr-line></aff><aff id="aff3"><label>3</label><addr-line>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Service de Neurologie, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Service de Neurologie, Hôpital Haut-Lévêque, Pessac, France</addr-line></aff><aff id="aff6"><label>6</label><addr-line>CHU Nantes, CIC0004, Service de Neurologie, Nantes, France</addr-line></aff><aff id="aff7"><label>7</label><addr-line>Unité 401, Pôle des Spécialités Neurologiques, Hôpital Neurologique Pierre Wertheimer, Bron, France</addr-line></aff><aff id="aff8"><label>8</label><addr-line>Département de Neurologie, CHU de Grenoble, Grenoble, France</addr-line></aff><aff id="aff9"><label>9</label><addr-line>Centre d’Investigation Clinique, Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, CHU Toulouse, Toulouse, France</addr-line></aff><aff id="aff10"><label>10</label><addr-line>EA2683, Service de Neurologie, Hôpital R. Salengro, CHRU de Lille, Lille, France</addr-line></aff><aff id="aff11"><label>11</label><addr-line>Pôle Tête-Cou-CETD, Service de Neurologie, Hôpitaux Universitaires, Strasbourg, France</addr-line></aff><aff id="aff12"><label>12</label><addr-line>INSERM, U763, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</addr-line></aff><aff id="aff13"><label>13</label><addr-line>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</addr-line></aff><author-notes><corresp>Dr A Brice, INSERM UMR_S679, Hôpital de la Salpêtrière, 47, Boulevard de l’Hôpital, 75651 Paris cedex 13, France; <email xlink:type="simple">alexis.brice@upmc.fr</email></corresp><fn fn-type="other"><p>Additional tables and figure are published online only at <ext-link ext-link-type="uri" xlink:href="http://jmg.bmj.com/content/vol46/issue7" xlink:type="simple">http://jmg.bmj.com/content/vol46/issue7</ext-link></p></fn><fn fn-type="other"><p>*The French Parkinson’s Disease Genetics Study Group members: Y Agid, A-M Bonnet, M Borg, A Brice, E Broussolle, Ph Damier, A Destée, A Dürr, F Durif, E Lohmann, M Martinez, C Penet, P Pollak, O Rascol, F Tison, C Tranchant, M Vérin, F Viallet, M Vidailhet</p></fn></author-notes><pub-date pub-type="ppub"><month>7</month><year>2009</year></pub-date><pub-date pub-type="epub-original"><day>8</day><month>4</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>8</day><month>4</month><year>2009</year></pub-date><volume>46</volume><volume-id pub-id-type="other">46</volume-id><volume-id pub-id-type="other">46</volume-id><issue>7</issue><issue-id pub-id-type="other">jmedgenet;46/7</issue-id><issue-id pub-id-type="other">7</issue-id><issue-id pub-id-type="other">46/7</issue-id><fpage>458</fpage><history><date date-type="received"><day>18</day><month>8</month><year>2008</year></date><date date-type="rev-recd"><day>6</day><month>1</month><year>2009</year></date><date date-type="accepted"><day>27</day><month>1</month><year>2009</year></date></history><permissions><copyright-statement>2009 BMJ Publishing Group Ltd</copyright-statement><copyright-year>2009</copyright-year></permissions><self-uri content-type="pdf" xlink:role="full-text" xlink:href="jmedgenet-46-458.pdf"></self-uri><abstract><sec><title>Background:</title><p>Mutations in the leucine-rich-repeat kinase 2 (<italic>LRRK2</italic>) gene have been identified in families with autosomal dominant Parkinson’s disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the <italic>LRRK2</italic> gene, few studies have analysed the entire gene in large series of ADPD families.</p></sec><sec><title>Methods:</title><p>We performed extensive mutation analyses of all 51 coding exons of the <italic>LRRK2</italic> gene in index cases from 226 Parkinson’s disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14).</p></sec><sec><title>Results:</title><p>We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein.</p></sec><sec><title>Conclusion:</title><p>This study leads us to conclude that <italic>LRRK2</italic> mutations are a common cause of autosomal dominant Parkinson’s disease in Europe and North Africa.</p></sec></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson’s disease</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson’s disease</title></titleInfo><name type="corporate"><namePart>for the French Parkinson’s Disease Genetics Study Group*</namePart></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Lesage</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Condroyer</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Lannuzel</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</affiliation><affiliation>Service de Neurologie, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E</namePart><namePart type="family">Lohmann</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Troiano</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">F</namePart><namePart type="family">Tison</namePart><affiliation>Service de Neurologie, Hôpital Haut-Lévêque, Pessac, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P</namePart><namePart type="family">Damier</namePart><affiliation>CHU Nantes, CIC0004, Service de Neurologie, Nantes, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Thobois</namePart><affiliation>Unité 401, Pôle des Spécialités Neurologiques, Hôpital Neurologique Pierre Wertheimer, Bron, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A-M</namePart><namePart type="family">Ouvrard-Hernandez</namePart><affiliation>Département de Neurologie, CHU de Grenoble, Grenoble, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Rivaud-Péchoux</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Brefel-Courbon</namePart><affiliation>Centre d’Investigation Clinique, Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, CHU Toulouse, Toulouse, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Destée</namePart><affiliation>EA2683, Service de Neurologie, Hôpital R. Salengro, CHRU de Lille, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Tranchant</namePart><affiliation>Pôle Tête-Cou-CETD, Service de Neurologie, Hôpitaux Universitaires, Strasbourg, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Romana</namePart><affiliation>INSERM, U763, Centre Hospitalier Universitaire, Pointe-à-Pitre, Guadeloupe</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Leclere</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Dürr</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Brice</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><affiliation>Université Pierre et Marie Curie-Paris6, UMR_S679, Pitié-Salpêtrière, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France</affiliation><affiliation>AP-HP, Groupe Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><genre>hwp-journal-coll</genre><topic>Genetic screening / counselling</topic></subject><originInfo><publisher>BMJ Publishing Group Ltd</publisher><dateIssued encoding="w3cdtf">2009-07</dateIssued><dateCreated encoding="w3cdtf">2009-04-08</dateCreated><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Background: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson’s disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. Methods: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson’s disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). Results: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. Conclusion: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson’s disease in Europe and North Africa.</abstract><note type="footnotes">Additional tables and figure are published online only at http://jmg.bmj.com/content/vol46/issue7</note><relatedItem type="host"><titleInfo><title>Journal of Medical Genetics</title></titleInfo><titleInfo type="abbreviated"><title>J Med Genet</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0022-2593</identifier><identifier type="eISSN">1468-6244</identifier><identifier type="PublisherID">jmg</identifier><identifier type="PublisherID-hwp">jmedgenet</identifier><identifier type="PublisherID-nlm-ta">J Med Genet</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>46</number></detail><detail type="issue"><caption>no.</caption><number>7</number></detail><extent unit="pages"><start>458</start></extent></part></relatedItem><identifier type="istex">D85D9436A64FCD3297283BD8AE39631C9AFCE5B4</identifier><identifier type="DOI">10.1136/jmg.2008.062612</identifier><identifier type="href">jmedgenet-46-458.pdf</identifier><identifier type="ArticleID">mg62612</identifier><identifier type="PMID">19357115</identifier><identifier type="local">jmedgenet;46/7/458</identifier><accessCondition type="use and reproduction" contentType="copyright">2009 BMJ Publishing Group Ltd</accessCondition><recordInfo><recordContentSource>BMJ</recordContentSource></recordInfo></mods></metadata><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/D85D9436A64FCD3297283BD8AE39631C9AFCE5B4/annexes/jpeg</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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