Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families
Identifieur interne : 000C64 ( Main/Corpus ); précédent : 000C63; suivant : 000C65Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families
Auteurs : Lianna Ishihara ; Rachel A. Gibson ; Liling Warren ; Rim Amouri ; Kelly Lyons ; Catherine Wielinski ; Christine Hunter ; Jina E. Swartz ; Ramu Elango ; P. Anthony Akkari ; David Leppert ; Linda Surh ; Kevin H. Reeves ; Siwan Thomas ; Leigh Ragone ; Nobutaka Hattori ; Rajesh Pahwa ; Joseph Jankovic ; Martha Nance ; Alan Freeman ; Neziha Gouider-Khouja ; Mounir Kefi ; Mourad Zouari ; Samia Ben Sassi ; Samia Ben Yahmed ; Ghada El Euch-Fayeche ; Lefkos Middleton ; David J. Burn ; Ray L. Watts ; Faycal HentatiSource :
- Movement Disorders [ 0885-3185 ] ; 2007-01.
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Abstract
Mutations in the leucine‐rich repeat kinase‐2 gene (LRRK2) are responsible for some forms of familial as well as sporadic Parkinson's disease (PD). The purpose of this study was to examine the frequency of a single pathogenic mutation (6055G>A) in the kinase domain of this gene in United States and Tunisian familial PD and to compare clinical characteristics between patients with and without the mutation. Standardized case report forms were used for clinical and demographic data collection. We investigated the frequency of the most common substitution of LRRK2 (G2019S, 6055G>A) and its impact on epidemiological and phenotypic features. The frequency of mutations in Tunisian families was 42% (38/91) and in U.S. families 2.6% (1/39), with the unique opportunity to compare homozygous (n = 23) and heterozygous (n = 109) Tunisian carriers of G2019S substitutions. Individuals with G2019S substitutions had an older age at onset but few other differences compared with families negative for the substitution. Patients with LRRK2 mutations had typical clinical features of PD. Comparisons between individuals with heterozygous and homozygous LRRK2 mutations suggested that gene dosage was not correlated with phenotypic differences; however, the estimated penetrance was greater in homozygotes across all age groups. © 2006 Movement Disorder Society
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DOI: 10.1002/mds.21180
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families</title><author><name sortKey="Ishihara, Lianna" sort="Ishihara, Lianna" uniqKey="Ishihara L" first="Lianna" last="Ishihara">Lianna Ishihara</name><affiliation><mods:affiliation>Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Gibson, Rachel A" sort="Gibson, Rachel A" uniqKey="Gibson R" first="Rachel A." last="Gibson">Rachel A. Gibson</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Warren, Liling" sort="Warren, Liling" uniqKey="Warren L" first="Liling" last="Warren">Liling Warren</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</mods:affiliation></affiliation></author><author><name sortKey="Amouri, Rim" sort="Amouri, Rim" uniqKey="Amouri R" first="Rim" last="Amouri">Rim Amouri</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Lyons, Kelly" sort="Lyons, Kelly" uniqKey="Lyons K" first="Kelly" last="Lyons">Kelly Lyons</name><affiliation><mods:affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</mods:affiliation></affiliation></author><author><name sortKey="Wielinski, Catherine" sort="Wielinski, Catherine" uniqKey="Wielinski C" first="Catherine" last="Wielinski">Catherine Wielinski</name><affiliation><mods:affiliation>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Hunter, Christine" sort="Hunter, Christine" uniqKey="Hunter C" first="Christine" last="Hunter">Christine Hunter</name><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Swartz, Jina E" sort="Swartz, Jina E" uniqKey="Swartz J" first="Jina E." last="Swartz">Jina E. Swartz</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Elango, Ramu" sort="Elango, Ramu" uniqKey="Elango R" first="Ramu" last="Elango">Ramu Elango</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Akkari, P Anthony" sort="Akkari, P Anthony" uniqKey="Akkari P" first="P. Anthony" last="Akkari">P. Anthony Akkari</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</mods:affiliation></affiliation></author><author><name sortKey="Leppert, David" sort="Leppert, David" uniqKey="Leppert D" first="David" last="Leppert">David Leppert</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Surh, Linda" sort="Surh, Linda" uniqKey="Surh L" first="Linda" last="Surh">Linda Surh</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Reeves, Kevin H" sort="Reeves, Kevin H" uniqKey="Reeves K" first="Kevin H." last="Reeves">Kevin H. Reeves</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</mods:affiliation></affiliation></author><author><name sortKey="Thomas, Siwan" sort="Thomas, Siwan" uniqKey="Thomas S" first="Siwan" last="Thomas">Siwan Thomas</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Ragone, Leigh" sort="Ragone, Leigh" uniqKey="Ragone L" first="Leigh" last="Ragone">Leigh Ragone</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</mods:affiliation></affiliation></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name><affiliation><mods:affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</mods:affiliation></affiliation></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name><affiliation><mods:affiliation>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Freeman, Alan" sort="Freeman, Alan" uniqKey="Freeman A" first="Alan" last="Freeman">Alan Freeman</name><affiliation><mods:affiliation>Department of Neurology, Emory University, Atlanta, Georgia, USA</mods:affiliation></affiliation></author><author><name sortKey="Gouider Houja, Neziha" sort="Gouider Houja, Neziha" uniqKey="Gouider Houja N" first="Neziha" last="Gouider-Khouja">Neziha Gouider-Khouja</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Kefi, Mounir" sort="Kefi, Mounir" uniqKey="Kefi M" first="Mounir" last="Kefi">Mounir Kefi</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Zouari, Mourad" sort="Zouari, Mourad" uniqKey="Zouari M" first="Mourad" last="Zouari">Mourad Zouari</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Ben Sassi, Samia" sort="Ben Sassi, Samia" uniqKey="Ben Sassi S" first="Samia" last="Ben Sassi">Samia Ben Sassi</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Ben Yahmed, Samia" sort="Ben Yahmed, Samia" uniqKey="Ben Yahmed S" first="Samia" last="Ben Yahmed">Samia Ben Yahmed</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="El Euch Ayeche, Ghada" sort="El Euch Ayeche, Ghada" uniqKey="El Euch Ayeche G" first="Ghada" last="El Euch-Fayeche">Ghada El Euch-Fayeche</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Middleton, Lefkos" sort="Middleton, Lefkos" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David J." last="Burn">David J. Burn</name><affiliation><mods:affiliation>Department of Neurology, Newcastle General Hospital, Newcastle‐upon‐Tyne, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray L." last="Watts">Ray L. Watts</name><affiliation><mods:affiliation>Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA</mods:affiliation></affiliation></author><author><name sortKey="Hentati, Faycal" sort="Hentati, Faycal" uniqKey="Hentati F" first="Faycal" last="Hentati">Faycal Hentati</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4</idno><date when="2007" year="2007">2007</date><idno type="doi">10.1002/mds.21180</idno><idno type="url">https://api.istex.fr/document/53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000C64</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families</title><author><name sortKey="Ishihara, Lianna" sort="Ishihara, Lianna" uniqKey="Ishihara L" first="Lianna" last="Ishihara">Lianna Ishihara</name><affiliation><mods:affiliation>Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Gibson, Rachel A" sort="Gibson, Rachel A" uniqKey="Gibson R" first="Rachel A." last="Gibson">Rachel A. Gibson</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Warren, Liling" sort="Warren, Liling" uniqKey="Warren L" first="Liling" last="Warren">Liling Warren</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</mods:affiliation></affiliation></author><author><name sortKey="Amouri, Rim" sort="Amouri, Rim" uniqKey="Amouri R" first="Rim" last="Amouri">Rim Amouri</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Lyons, Kelly" sort="Lyons, Kelly" uniqKey="Lyons K" first="Kelly" last="Lyons">Kelly Lyons</name><affiliation><mods:affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</mods:affiliation></affiliation></author><author><name sortKey="Wielinski, Catherine" sort="Wielinski, Catherine" uniqKey="Wielinski C" first="Catherine" last="Wielinski">Catherine Wielinski</name><affiliation><mods:affiliation>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Hunter, Christine" sort="Hunter, Christine" uniqKey="Hunter C" first="Christine" last="Hunter">Christine Hunter</name><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Swartz, Jina E" sort="Swartz, Jina E" uniqKey="Swartz J" first="Jina E." last="Swartz">Jina E. Swartz</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Elango, Ramu" sort="Elango, Ramu" uniqKey="Elango R" first="Ramu" last="Elango">Ramu Elango</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Akkari, P Anthony" sort="Akkari, P Anthony" uniqKey="Akkari P" first="P. Anthony" last="Akkari">P. Anthony Akkari</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</mods:affiliation></affiliation></author><author><name sortKey="Leppert, David" sort="Leppert, David" uniqKey="Leppert D" first="David" last="Leppert">David Leppert</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Surh, Linda" sort="Surh, Linda" uniqKey="Surh L" first="Linda" last="Surh">Linda Surh</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Reeves, Kevin H" sort="Reeves, Kevin H" uniqKey="Reeves K" first="Kevin H." last="Reeves">Kevin H. Reeves</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</mods:affiliation></affiliation></author><author><name sortKey="Thomas, Siwan" sort="Thomas, Siwan" uniqKey="Thomas S" first="Siwan" last="Thomas">Siwan Thomas</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Ragone, Leigh" sort="Ragone, Leigh" uniqKey="Ragone L" first="Leigh" last="Ragone">Leigh Ragone</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</mods:affiliation></affiliation></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name><affiliation><mods:affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</mods:affiliation></affiliation></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</mods:affiliation></affiliation></author><author><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name><affiliation><mods:affiliation>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Freeman, Alan" sort="Freeman, Alan" uniqKey="Freeman A" first="Alan" last="Freeman">Alan Freeman</name><affiliation><mods:affiliation>Department of Neurology, Emory University, Atlanta, Georgia, USA</mods:affiliation></affiliation></author><author><name sortKey="Gouider Houja, Neziha" sort="Gouider Houja, Neziha" uniqKey="Gouider Houja N" first="Neziha" last="Gouider-Khouja">Neziha Gouider-Khouja</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Kefi, Mounir" sort="Kefi, Mounir" uniqKey="Kefi M" first="Mounir" last="Kefi">Mounir Kefi</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Zouari, Mourad" sort="Zouari, Mourad" uniqKey="Zouari M" first="Mourad" last="Zouari">Mourad Zouari</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Ben Sassi, Samia" sort="Ben Sassi, Samia" uniqKey="Ben Sassi S" first="Samia" last="Ben Sassi">Samia Ben Sassi</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Ben Yahmed, Samia" sort="Ben Yahmed, Samia" uniqKey="Ben Yahmed S" first="Samia" last="Ben Yahmed">Samia Ben Yahmed</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="El Euch Ayeche, Ghada" sort="El Euch Ayeche, Ghada" uniqKey="El Euch Ayeche G" first="Ghada" last="El Euch-Fayeche">Ghada El Euch-Fayeche</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author><author><name sortKey="Middleton, Lefkos" sort="Middleton, Lefkos" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name><affiliation><mods:affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David J." last="Burn">David J. Burn</name><affiliation><mods:affiliation>Department of Neurology, Newcastle General Hospital, Newcastle‐upon‐Tyne, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray L." last="Watts">Ray L. Watts</name><affiliation><mods:affiliation>Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA</mods:affiliation></affiliation></author><author><name sortKey="Hentati, Faycal" sort="Hentati, Faycal" uniqKey="Hentati F" first="Faycal" last="Hentati">Faycal Hentati</name><affiliation><mods:affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-01">2007-01</date><biblScope unit="volume">22</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="55">55</biblScope><biblScope unit="page" to="61">61</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4</idno><idno type="DOI">10.1002/mds.21180</idno><idno type="ArticleID">MDS21180</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>G2019S</term><term>LRRK2</term><term>PARK8</term><term>Parkinson disease</term><term>genetics</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in the leucine‐rich repeat kinase‐2 gene (LRRK2) are responsible for some forms of familial as well as sporadic Parkinson's disease (PD). The purpose of this study was to examine the frequency of a single pathogenic mutation (6055G>A) in the kinase domain of this gene in United States and Tunisian familial PD and to compare clinical characteristics between patients with and without the mutation. Standardized case report forms were used for clinical and demographic data collection. We investigated the frequency of the most common substitution of LRRK2 (G2019S, 6055G>A) and its impact on epidemiological and phenotypic features. The frequency of mutations in Tunisian families was 42% (38/91) and in U.S. families 2.6% (1/39), with the unique opportunity to compare homozygous (n = 23) and heterozygous (n = 109) Tunisian carriers of G2019S substitutions. Individuals with G2019S substitutions had an older age at onset but few other differences compared with families negative for the substitution. Patients with LRRK2 mutations had typical clinical features of PD. Comparisons between individuals with heterozygous and homozygous LRRK2 mutations suggested that gene dosage was not correlated with phenotypic differences; however, the estimated penetrance was greater in homozygotes across all age groups. © 2006 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Lianna Ishihara Mphil</name><affiliations><json:string>Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</json:string></affiliations></json:item><json:item><name>Rachel A. Gibson PhD</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</json:string></affiliations></json:item><json:item><name>Liling Warren PhD</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</json:string></affiliations></json:item><json:item><name>Rim Amouri PhD</name><affiliations><json:string>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</json:string></affiliations></json:item><json:item><name>Kelly Lyons PhD</name><affiliations><json:string>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</json:string></affiliations></json:item><json:item><name>Catherine Wielinski MPH</name><affiliations><json:string>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</json:string></affiliations></json:item><json:item><name>Christine Hunter RN, CCRC</name><affiliations><json:string>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>Jina E. Swartz MD, PhD</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</json:string></affiliations></json:item><json:item><name>Ramu Elango PhD</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</json:string></affiliations></json:item><json:item><name>P. Anthony Akkari PhD</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</json:string></affiliations></json:item><json:item><name>David Leppert MD</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</json:string></affiliations></json:item><json:item><name>Linda Surh MD, PhD</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</json:string></affiliations></json:item><json:item><name>Kevin H. Reeves BSc</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</json:string></affiliations></json:item><json:item><name>Siwan Thomas BSc</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</json:string></affiliations></json:item><json:item><name>Leigh Ragone MSc</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</json:string></affiliations></json:item><json:item><name>Nobutaka Hattori MD, PhD</name><affiliations><json:string>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Rajesh Pahwa MD</name><affiliations><json:string>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</json:string></affiliations></json:item><json:item><name>Joseph Jankovic MD</name><affiliations><json:string>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>Martha Nance MD</name><affiliations><json:string>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</json:string></affiliations></json:item><json:item><name>Alan Freeman MD</name><affiliations><json:string>Department of Neurology, Emory University, Atlanta, Georgia, USA</json:string></affiliations></json:item><json:item><name>Neziha Gouider‐Khouja MD</name><affiliations><json:string>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</json:string></affiliations></json:item><json:item><name>Mounir Kefi MD</name><affiliations><json:string>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</json:string></affiliations></json:item><json:item><name>Mourad Zouari MD</name><affiliations><json:string>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</json:string></affiliations></json:item><json:item><name>Samia Ben Sassi MD</name><affiliations><json:string>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</json:string></affiliations></json:item><json:item><name>Samia Ben Yahmed MD</name><affiliations><json:string>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</json:string></affiliations></json:item><json:item><name>Ghada El Euch‐Fayeche MD</name><affiliations><json:string>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</json:string></affiliations></json:item><json:item><name>Lefkos Middleton MD</name><affiliations><json:string>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</json:string></affiliations></json:item><json:item><name>David J. Burn MD</name><affiliations><json:string>Department of Neurology, Newcastle General Hospital, Newcastle‐upon‐Tyne, United Kingdom</json:string></affiliations></json:item><json:item><name>Ray L. Watts MD</name><affiliations><json:string>Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA</json:string></affiliations></json:item><json:item><name>Faycal Hentati MD</name><affiliations><json:string>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>genetics</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LRRK2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>G2019S</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PARK8</value></json:item></subject><articleId><json:string>MDS21180</json:string></articleId><language><json:string>eng</json:string></language><abstract>Mutations in the leucine‐rich repeat kinase‐2 gene (LRRK2) are responsible for some forms of familial as well as sporadic Parkinson's disease (PD). The purpose of this study was to examine the frequency of a single pathogenic mutation (6055G>A) in the kinase domain of this gene in United States and Tunisian familial PD and to compare clinical characteristics between patients with and without the mutation. Standardized case report forms were used for clinical and demographic data collection. We investigated the frequency of the most common substitution of LRRK2 (G2019S, 6055G>A) and its impact on epidemiological and phenotypic features. The frequency of mutations in Tunisian families was 42% (38/91) and in U.S. families 2.6% (1/39), with the unique opportunity to compare homozygous (n = 23) and heterozygous (n = 109) Tunisian carriers of G2019S substitutions. Individuals with G2019S substitutions had an older age at onset but few other differences compared with families negative for the substitution. Patients with LRRK2 mutations had typical clinical features of PD. Comparisons between individuals with heterozygous and homozygous LRRK2 mutations suggested that gene dosage was not correlated with phenotypic differences; however, the estimated penetrance was greater in homozygotes across all age groups. © 2006 Movement Disorder Society</abstract><qualityIndicators><score>6.169</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1354</abstractCharCount><pdfWordCount>3769</pdfWordCount><pdfCharCount>24610</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>200</abstractWordCount></qualityIndicators><title>Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families</title><genre><json:string>article</json:string></genre><host><volume>22</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>7</total><last>61</last><first>55</first></pages><issn><json:string>0885-3185</json:string></issn><issue>1</issue><subject><json:item><value>Research Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8257</json:string></eissn><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><publicationDate>2007</publicationDate><copyrightDate>2007</copyrightDate><doi><json:string>10.1002/mds.21180</json:string></doi><id>53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2007</date></publicationStmt><notesStmt><note>GlaxoSmithKline Pharmaceuticals</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families</title><author><persName><forename type="first">Lianna</forename><surname>Ishihara</surname></persName><roleName type="degree">Mphil</roleName><note type="correspondence"><p>Correspondence: University of Cambridge, Department of Public Health and Primary Care, Institute of Public Health, Forvie Site, Robinson Way, Cambridge CB2 2SR, United Kingdom</p></note><affiliation>Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</affiliation></author><author><persName><forename type="first">Rachel A.</forename><surname>Gibson</surname></persName><roleName type="degree">PhD</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation></author><author><persName><forename type="first">Liling</forename><surname>Warren</surname></persName><roleName type="degree">PhD</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</affiliation></author><author><persName><forename type="first">Rim</forename><surname>Amouri</surname></persName><roleName type="degree">PhD</roleName><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation></author><author><persName><forename type="first">Kelly</forename><surname>Lyons</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</affiliation></author><author><persName><forename type="first">Catherine</forename><surname>Wielinski</surname></persName><roleName type="degree">MPH</roleName><affiliation>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</affiliation></author><author><persName><forename type="first">Christine</forename><surname>Hunter</surname></persName><roleName type="degree">RN, CCRC</roleName><affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">Jina E.</forename><surname>Swartz</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation></author><author><persName><forename type="first">Ramu</forename><surname>Elango</surname></persName><roleName type="degree">PhD</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation></author><author><persName><forename type="first">P. Anthony</forename><surname>Akkari</surname></persName><roleName type="degree">PhD</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</affiliation></author><author><persName><forename type="first">David</forename><surname>Leppert</surname></persName><roleName type="degree">MD</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation></author><author><persName><forename type="first">Linda</forename><surname>Surh</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation></author><author><persName><forename type="first">Kevin H.</forename><surname>Reeves</surname></persName><roleName type="degree">BSc</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</affiliation></author><author><persName><forename type="first">Siwan</forename><surname>Thomas</surname></persName><roleName type="degree">BSc</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation></author><author><persName><forename type="first">Leigh</forename><surname>Ragone</surname></persName><roleName type="degree">MSc</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</affiliation></author><author><persName><forename type="first">Nobutaka</forename><surname>Hattori</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Rajesh</forename><surname>Pahwa</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</affiliation></author><author><persName><forename type="first">Joseph</forename><surname>Jankovic</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">Martha</forename><surname>Nance</surname></persName><roleName type="degree">MD</roleName><affiliation>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</affiliation></author><author><persName><forename type="first">Alan</forename><surname>Freeman</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Emory University, Atlanta, Georgia, USA</affiliation></author><author><persName><forename type="first">Neziha</forename><surname>Gouider‐Khouja</surname></persName><roleName type="degree">MD</roleName><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation></author><author><persName><forename type="first">Mounir</forename><surname>Kefi</surname></persName><roleName type="degree">MD</roleName><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation></author><author><persName><forename type="first">Mourad</forename><surname>Zouari</surname></persName><roleName type="degree">MD</roleName><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation></author><author><persName><forename type="first">Samia</forename><surname>Ben Sassi</surname></persName><roleName type="degree">MD</roleName><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation></author><author><persName><forename type="first">Samia</forename><surname>Ben Yahmed</surname></persName><roleName type="degree">MD</roleName><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation></author><author><persName><forename type="first">Ghada</forename><surname>El Euch‐Fayeche</surname></persName><roleName type="degree">MD</roleName><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation></author><author><persName><forename type="first">Lefkos</forename><surname>Middleton</surname></persName><roleName type="degree">MD</roleName><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation></author><author><persName><forename type="first">David J.</forename><surname>Burn</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Newcastle General Hospital, Newcastle‐upon‐Tyne, United Kingdom</affiliation></author><author><persName><forename type="first">Ray L.</forename><surname>Watts</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA</affiliation></author><author><persName><forename type="first">Faycal</forename><surname>Hentati</surname></persName><roleName type="degree">MD</roleName><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-01"></date><biblScope unit="volume">22</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="55">55</biblScope><biblScope unit="page" to="61">61</biblScope></imprint></monogr><idno type="istex">53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4</idno><idno type="DOI">10.1002/mds.21180</idno><idno type="ArticleID">MDS21180</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2007</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Mutations in the leucine‐rich repeat kinase‐2 gene (LRRK2) are responsible for some forms of familial as well as sporadic Parkinson's disease (PD). The purpose of this study was to examine the frequency of a single pathogenic mutation (6055G>A) in the kinase domain of this gene in United States and Tunisian familial PD and to compare clinical characteristics between patients with and without the mutation. Standardized case report forms were used for clinical and demographic data collection. We investigated the frequency of the most common substitution of LRRK2 (G2019S, 6055G>A) and its impact on epidemiological and phenotypic features. The frequency of mutations in Tunisian families was 42% (38/91) and in U.S. families 2.6% (1/39), with the unique opportunity to compare homozygous (n = 23) and heterozygous (n = 109) Tunisian carriers of G2019S substitutions. Individuals with G2019S substitutions had an older age at onset but few other differences compared with families negative for the substitution. Patients with LRRK2 mutations had typical clinical features of PD. Comparisons between individuals with heterozygous and homozygous LRRK2 mutations suggested that gene dosage was not correlated with phenotypic differences; however, the estimated penetrance was greater in homozygotes across all age groups. © 2006 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson disease</term></item><item><term>genetics</term></item><item><term>LRRK2</term></item><item><term>G2019S</term></item><item><term>PARK8</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2006-04-24">Received</change><change when="2006-07-20">Registration</change><change when="2007-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. 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affiliationRef="#af4"><personName><givenNames>Samia</givenNames><familyName>Ben Yahmed</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au26" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Ghada</givenNames><familyName>El Euch‐Fayeche</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au27" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Lefkos</givenNames><familyName>Middleton</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au28" creatorRole="author" affiliationRef="#af10"><personName><givenNames>David J.</givenNames><familyName>Burn</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au29" creatorRole="author" affiliationRef="#af11"><personName><givenNames>Ray L.</givenNames><familyName>Watts</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au30" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Faycal</givenNames><familyName>Hentati</familyName><degrees>MD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="GB" type="organization"><unparsedAffiliation>Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="GB" type="organization"><unparsedAffiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="TN" type="organization"><unparsedAffiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="US" type="organization"><unparsedAffiliation>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="JP" type="organization"><unparsedAffiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Emory University, Atlanta, Georgia, USA</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="GB" type="organization"><unparsedAffiliation>Department of Neurology, Newcastle General Hospital, Newcastle‐upon‐Tyne, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson disease</keyword><keyword xml:id="kwd2">genetics</keyword><keyword xml:id="kwd3">LRRK2</keyword><keyword xml:id="kwd4">G2019S</keyword><keyword xml:id="kwd5">PARK8</keyword></keywordGroup><fundingInfo><fundingAgency>GlaxoSmithKline Pharmaceuticals</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Mutations in the leucine‐rich repeat kinase‐2 gene (<i>LRRK2</i>) are responsible for some forms of familial as well as sporadic Parkinson's disease (PD). The purpose of this study was to examine the frequency of a single pathogenic mutation (6055G>A) in the kinase domain of this gene in United States and Tunisian familial PD and to compare clinical characteristics between patients with and without the mutation. Standardized case report forms were used for clinical and demographic data collection. We investigated the frequency of the most common substitution of <i>LRRK2</i> (G2019S, 6055G>A) and its impact on epidemiological and phenotypic features. The frequency of mutations in Tunisian families was 42% (38/91) and in U.S. families 2.6% (1/39), with the unique opportunity to compare homozygous (n = 23) and heterozygous (n = 109) Tunisian carriers of G2019S substitutions. Individuals with G2019S substitutions had an older age at onset but few other differences compared with families negative for the substitution. Patients with <i>LRRK2</i> mutations had typical clinical features of PD. Comparisons between individuals with heterozygous and homozygous <i>LRRK2</i> mutations suggested that gene dosage was not correlated with phenotypic differences; however, the estimated penetrance was greater in homozygotes across all age groups. © 2006 Movement Disorder Society</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>G2019S LRRK2 Mutation in Parkinson's</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families</title></titleInfo><name type="personal"><namePart type="given">Lianna</namePart><namePart type="family">Ishihara</namePart><namePart type="termsOfAddress">Mphil</namePart><affiliation>Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</affiliation><description>Correspondence: University of Cambridge, Department of Public Health and Primary Care, Institute of Public Health, Forvie Site, Robinson Way, Cambridge CB2 2SR, United Kingdom</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rachel A.</namePart><namePart type="family">Gibson</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Liling</namePart><namePart type="family">Warren</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rim</namePart><namePart type="family">Amouri</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kelly</namePart><namePart type="family">Lyons</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Catherine</namePart><namePart type="family">Wielinski</namePart><namePart type="termsOfAddress">MPH</namePart><affiliation>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Hunter</namePart><namePart type="termsOfAddress">RN, CCRC</namePart><affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jina E.</namePart><namePart type="family">Swartz</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ramu</namePart><namePart type="family">Elango</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P. Anthony</namePart><namePart type="family">Akkari</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David</namePart><namePart type="family">Leppert</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Linda</namePart><namePart type="family">Surh</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kevin H.</namePart><namePart type="family">Reeves</namePart><namePart type="termsOfAddress">BSc</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Siwan</namePart><namePart type="family">Thomas</namePart><namePart type="termsOfAddress">BSc</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Leigh</namePart><namePart type="family">Ragone</namePart><namePart type="termsOfAddress">MSc</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nobutaka</namePart><namePart type="family">Hattori</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rajesh</namePart><namePart type="family">Pahwa</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joseph</namePart><namePart type="family">Jankovic</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Martha</namePart><namePart type="family">Nance</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Struthers Parkinson's Center, Golden Valley, Minnesota, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alan</namePart><namePart type="family">Freeman</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Emory University, Atlanta, Georgia, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Neziha</namePart><namePart type="family">Gouider‐Khouja</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mounir</namePart><namePart type="family">Kefi</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mourad</namePart><namePart type="family">Zouari</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Samia</namePart><namePart type="family">Ben Sassi</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Samia</namePart><namePart type="family">Ben Yahmed</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ghada</namePart><namePart type="family">El Euch‐Fayeche</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lefkos</namePart><namePart type="family">Middleton</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David J.</namePart><namePart type="family">Burn</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Newcastle General Hospital, Newcastle‐upon‐Tyne, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ray L.</namePart><namePart type="family">Watts</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Faycal</namePart><namePart type="family">Hentati</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis, Tunisia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2007-01</dateIssued><dateCaptured encoding="w3cdtf">2006-04-24</dateCaptured><dateValid encoding="w3cdtf">2006-07-20</dateValid><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">1</extent><extent unit="tables">3</extent><extent unit="references">35</extent><extent unit="words">4393</extent></physicalDescription><abstract lang="en">Mutations in the leucine‐rich repeat kinase‐2 gene (LRRK2) are responsible for some forms of familial as well as sporadic Parkinson's disease (PD). The purpose of this study was to examine the frequency of a single pathogenic mutation (6055G>A) in the kinase domain of this gene in United States and Tunisian familial PD and to compare clinical characteristics between patients with and without the mutation. Standardized case report forms were used for clinical and demographic data collection. We investigated the frequency of the most common substitution of LRRK2 (G2019S, 6055G>A) and its impact on epidemiological and phenotypic features. The frequency of mutations in Tunisian families was 42% (38/91) and in U.S. families 2.6% (1/39), with the unique opportunity to compare homozygous (n = 23) and heterozygous (n = 109) Tunisian carriers of G2019S substitutions. Individuals with G2019S substitutions had an older age at onset but few other differences compared with families negative for the substitution. Patients with LRRK2 mutations had typical clinical features of PD. Comparisons between individuals with heterozygous and homozygous LRRK2 mutations suggested that gene dosage was not correlated with phenotypic differences; however, the estimated penetrance was greater in homozygotes across all age groups. © 2006 Movement Disorder Society</abstract><note type="funding">GlaxoSmithKline Pharmaceuticals</note><subject lang="en"><genre>Keywords</genre><topic>Parkinson disease</topic><topic>genetics</topic><topic>LRRK2</topic><topic>G2019S</topic><topic>PARK8</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>22</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>55</start><end>61</end><total>7</total></extent></part></relatedItem><identifier type="istex">53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4</identifier><identifier type="DOI">10.1002/mds.21180</identifier><identifier type="ArticleID">MDS21180</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2006 Movement Disorder Society</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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