Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families
Identifieur interne : 003B11 ( Main/Merge ); précédent : 003B10; suivant : 003B12Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families
Auteurs : Lianna Ishihara [Royaume-Uni] ; Rachel A. Gibson [Royaume-Uni] ; Liling Warren [États-Unis] ; Rim Amouri [Tunisie] ; Kelly Lyons [États-Unis] ; Catherine Wielinski [États-Unis] ; Christine Hunter [États-Unis] ; Jina E. Swartz [Royaume-Uni] ; Ramu Elango [Royaume-Uni] ; P. Anthony Akkari [États-Unis] ; David Leppert [Royaume-Uni] ; Linda Surh [Royaume-Uni] ; Kevin H. Reeves [États-Unis] ; Siwan Thomas [Royaume-Uni] ; Leigh Ragone [États-Unis] ; Nobutaka Hattori [Japon] ; Rajesh Pahwa [États-Unis] ; Joseph Jankovic [États-Unis] ; Martha Nance [États-Unis] ; Alan Freeman [États-Unis] ; Neziha Gouider-Khouja [Tunisie] ; Mounir Kefi [Tunisie] ; Mourad Zouari [Tunisie] ; Samia Ben Sassi [Tunisie] ; Samia Ben Yahmed [Tunisie] ; Ghada El Euch-Fayeche [Tunisie] ; Lefkos Middleton [Royaume-Uni] ; David J. Burn [Royaume-Uni] ; Ray L. Watts [États-Unis] ; Faycal Hentati [Tunisie]Source :
- Movement Disorders [ 0885-3185 ] ; 2007-01.
Descripteurs français
- Wicri :
- geographic : Tunisie.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Cross-Cultural Comparison, DNA Mutational Analysis, European Continental Ancestry Group, Family Health, Female, G2019S, Genetic Testing (methods), Genotype, Glycine (genetics), Humans, LRRK2, Male, Middle Aged, Mutation (genetics), North America (epidemiology), North America (ethnology), PARK8, Parkinson Disease (epidemiology), Parkinson Disease (genetics), Parkinson disease, Protein-Serine-Threonine Kinases (genetics), Serine (genetics), Tunisia (epidemiology), Tunisia (ethnology), genetics.
- MESH :
- chemical , genetics : Glycine, Protein-Serine-Threonine Kinases, Serine.
- geographic , epidemiology : North America, Tunisia.
- geographic , ethnology : North America, Tunisia.
- epidemiology : Parkinson Disease.
- genetics : Mutation, Parkinson Disease.
- methods : Genetic Testing.
- Adult, Aged, Aged, 80 and over, Cross-Cultural Comparison, DNA Mutational Analysis, European Continental Ancestry Group, Family Health, Female, Genotype, Humans, Male, Middle Aged.
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
Url:
DOI: 10.1002/mds.21180
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ISTEX:53A067ADB2FD6E36EC54AC61A38B5846E4B4FCE4Le document en format XML
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<author><name sortKey="Hunter, Christine" sort="Hunter, Christine" uniqKey="Hunter C" first="Christine" last="Hunter">Christine Hunter</name>
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<author><name sortKey="Swartz, Jina E" sort="Swartz, Jina E" uniqKey="Swartz J" first="Jina E." last="Swartz">Jina E. Swartz</name>
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<author><name sortKey="Elango, Ramu" sort="Elango, Ramu" uniqKey="Elango R" first="Ramu" last="Elango">Ramu Elango</name>
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<author><name sortKey="Akkari, P Anthony" sort="Akkari, P Anthony" uniqKey="Akkari P" first="P. Anthony" last="Akkari">P. Anthony Akkari</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
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<author><name sortKey="Leppert, David" sort="Leppert, David" uniqKey="Leppert D" first="David" last="Leppert">David Leppert</name>
<affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
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<author><name sortKey="Surh, Linda" sort="Surh, Linda" uniqKey="Surh L" first="Linda" last="Surh">Linda Surh</name>
<affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</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 wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
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</author>
<author><name sortKey="Thomas, Siwan" sort="Thomas, Siwan" uniqKey="Thomas S" first="Siwan" last="Thomas">Siwan Thomas</name>
<affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ragone, Leigh" sort="Ragone, Leigh" uniqKey="Ragone L" first="Leigh" last="Ragone">Leigh Ragone</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name>
<affiliation wicri:level="3"><country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Neurology, Juntendo University School of Medicine, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas</wicri:regionArea>
<placeName><region type="state">Kansas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Baylor College of Medicine, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
<placeName><settlement type="city">Houston</settlement>
<region type="state">Texas</region>
</placeName>
<orgName type="university" n="3">Baylor College of Medicine</orgName>
</affiliation>
</author>
<author><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Struthers Parkinson's Center, Golden Valley, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Freeman, Alan" sort="Freeman, Alan" uniqKey="Freeman A" first="Alan" last="Freeman">Alan Freeman</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Emory University, Atlanta, Georgia</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</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 wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kefi, Mounir" sort="Kefi, Mounir" uniqKey="Kefi M" first="Mounir" last="Kefi">Mounir Kefi</name>
<affiliation wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zouari, Mourad" sort="Zouari, Mourad" uniqKey="Zouari M" first="Mourad" last="Zouari">Mourad Zouari</name>
<affiliation wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Middleton, Lefkos" sort="Middleton, Lefkos" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name>
<affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Neurology, Newcastle General Hospital, Newcastle‐upon‐Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle‐upon‐Tyne</wicri:noRegion>
</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 wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama</wicri:regionArea>
<placeName><region type="state">Alabama</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hentati, Faycal" sort="Hentati, Faycal" uniqKey="Hentati F" first="Faycal" last="Hentati">Faycal Hentati</name>
<affiliation wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</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="vol">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>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Cross-Cultural Comparison</term>
<term>DNA Mutational Analysis</term>
<term>European Continental Ancestry Group</term>
<term>Family Health</term>
<term>Female</term>
<term>G2019S</term>
<term>Genetic Testing (methods)</term>
<term>Genotype</term>
<term>Glycine (genetics)</term>
<term>Humans</term>
<term>LRRK2</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Mutation (genetics)</term>
<term>North America (epidemiology)</term>
<term>North America (ethnology)</term>
<term>PARK8</term>
<term>Parkinson Disease (epidemiology)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson disease</term>
<term>Protein-Serine-Threonine Kinases (genetics)</term>
<term>Serine (genetics)</term>
<term>Tunisia (epidemiology)</term>
<term>Tunisia (ethnology)</term>
<term>genetics</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glycine</term>
<term>Protein-Serine-Threonine Kinases</term>
<term>Serine</term>
</keywords>
<keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en"><term>North America</term>
<term>Tunisia</term>
</keywords>
<keywords scheme="MESH" type="geographic" qualifier="ethnology" xml:lang="en"><term>North America</term>
<term>Tunisia</term>
</keywords>
<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mutation</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Genetic Testing</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Cross-Cultural Comparison</term>
<term>DNA Mutational Analysis</term>
<term>European Continental Ancestry Group</term>
<term>Family Health</term>
<term>Female</term>
<term>Genotype</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
</keywords>
<keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Tunisie</term>
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<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>
<double doi="10.1002/mds.21180"><ISTEX><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>
</author>
<author><name sortKey="Gibson, Rachel A" sort="Gibson, Rachel A" uniqKey="Gibson R" first="Rachel A." last="Gibson">Rachel A. Gibson</name>
</author>
<author><name sortKey="Warren, Liling" sort="Warren, Liling" uniqKey="Warren L" first="Liling" last="Warren">Liling Warren</name>
</author>
<author><name sortKey="Amouri, Rim" sort="Amouri, Rim" uniqKey="Amouri R" first="Rim" last="Amouri">Rim Amouri</name>
</author>
<author><name sortKey="Lyons, Kelly" sort="Lyons, Kelly" uniqKey="Lyons K" first="Kelly" last="Lyons">Kelly Lyons</name>
</author>
<author><name sortKey="Wielinski, Catherine" sort="Wielinski, Catherine" uniqKey="Wielinski C" first="Catherine" last="Wielinski">Catherine Wielinski</name>
</author>
<author><name sortKey="Hunter, Christine" sort="Hunter, Christine" uniqKey="Hunter C" first="Christine" last="Hunter">Christine Hunter</name>
</author>
<author><name sortKey="Swartz, Jina E" sort="Swartz, Jina E" uniqKey="Swartz J" first="Jina E." last="Swartz">Jina E. Swartz</name>
</author>
<author><name sortKey="Elango, Ramu" sort="Elango, Ramu" uniqKey="Elango R" first="Ramu" last="Elango">Ramu Elango</name>
</author>
<author><name sortKey="Akkari, P Anthony" sort="Akkari, P Anthony" uniqKey="Akkari P" first="P. Anthony" last="Akkari">P. Anthony Akkari</name>
</author>
<author><name sortKey="Leppert, David" sort="Leppert, David" uniqKey="Leppert D" first="David" last="Leppert">David Leppert</name>
</author>
<author><name sortKey="Surh, Linda" sort="Surh, Linda" uniqKey="Surh L" first="Linda" last="Surh">Linda Surh</name>
</author>
<author><name sortKey="Reeves, Kevin H" sort="Reeves, Kevin H" uniqKey="Reeves K" first="Kevin H." last="Reeves">Kevin H. Reeves</name>
</author>
<author><name sortKey="Thomas, Siwan" sort="Thomas, Siwan" uniqKey="Thomas S" first="Siwan" last="Thomas">Siwan Thomas</name>
</author>
<author><name sortKey="Ragone, Leigh" sort="Ragone, Leigh" uniqKey="Ragone L" first="Leigh" last="Ragone">Leigh Ragone</name>
</author>
<author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name>
</author>
<author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation><country>États-Unis</country>
<placeName><settlement type="city">Houston</settlement>
<region type="state">Texas</region>
</placeName>
<orgName type="university" n="3">Baylor College of Medicine</orgName>
</affiliation>
</author>
<author><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name>
</author>
<author><name sortKey="Freeman, Alan" sort="Freeman, Alan" uniqKey="Freeman A" first="Alan" last="Freeman">Alan Freeman</name>
</author>
<author><name sortKey="Gouider Houja, Neziha" sort="Gouider Houja, Neziha" uniqKey="Gouider Houja N" first="Neziha" last="Gouider-Khouja">Neziha Gouider-Khouja</name>
</author>
<author><name sortKey="Kefi, Mounir" sort="Kefi, Mounir" uniqKey="Kefi M" first="Mounir" last="Kefi">Mounir Kefi</name>
</author>
<author><name sortKey="Zouari, Mourad" sort="Zouari, Mourad" uniqKey="Zouari M" first="Mourad" last="Zouari">Mourad Zouari</name>
</author>
<author><name sortKey="Ben Sassi, Samia" sort="Ben Sassi, Samia" uniqKey="Ben Sassi S" first="Samia" last="Ben Sassi">Samia Ben Sassi</name>
</author>
<author><name sortKey="Ben Yahmed, Samia" sort="Ben Yahmed, Samia" uniqKey="Ben Yahmed S" first="Samia" last="Ben Yahmed">Samia Ben Yahmed</name>
</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>
</author>
<author><name sortKey="Middleton, Lefkos" sort="Middleton, Lefkos" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name>
</author>
<author><name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David J." last="Burn">David J. Burn</name>
</author>
<author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray L." last="Watts">Ray L. Watts</name>
</author>
<author><name sortKey="Hentati, Faycal" sort="Hentati, Faycal" uniqKey="Hentati F" first="Faycal" last="Hentati">Faycal Hentati</name>
</author>
</titleStmt>
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<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 wicri:level="4"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Public Health and Primary Care, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</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 wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Warren, Liling" sort="Warren, Liling" uniqKey="Warren L" first="Liling" last="Warren">Liling Warren</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Amouri, Rim" sort="Amouri, Rim" uniqKey="Amouri R" first="Rim" last="Amouri">Rim Amouri</name>
<affiliation wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lyons, Kelly" sort="Lyons, Kelly" uniqKey="Lyons K" first="Kelly" last="Lyons">Kelly Lyons</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas</wicri:regionArea>
<placeName><region type="state">Kansas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wielinski, Catherine" sort="Wielinski, Catherine" uniqKey="Wielinski C" first="Catherine" last="Wielinski">Catherine Wielinski</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Struthers Parkinson's Center, Golden Valley, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hunter, Christine" sort="Hunter, Christine" uniqKey="Hunter C" first="Christine" last="Hunter">Christine Hunter</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Baylor College of Medicine, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</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 wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Elango, Ramu" sort="Elango, Ramu" uniqKey="Elango R" first="Ramu" last="Elango">Ramu Elango</name>
<affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</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 wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Leppert, David" sort="Leppert, David" uniqKey="Leppert D" first="David" last="Leppert">David Leppert</name>
<affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Surh, Linda" sort="Surh, Linda" uniqKey="Surh L" first="Linda" last="Surh">Linda Surh</name>
<affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</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 wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Thomas, Siwan" sort="Thomas, Siwan" uniqKey="Thomas S" first="Siwan" last="Thomas">Siwan Thomas</name>
<affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ragone, Leigh" sort="Ragone, Leigh" uniqKey="Ragone L" first="Leigh" last="Ragone">Leigh Ragone</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name>
<affiliation wicri:level="3"><country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Neurology, Juntendo University School of Medicine, Tokyo</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas</wicri:regionArea>
<placeName><region type="state">Kansas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Baylor College of Medicine, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
<placeName><settlement type="city">Houston</settlement>
<region type="state">Texas</region>
</placeName>
<orgName type="university" n="3">Baylor College of Medicine</orgName>
</affiliation>
</author>
<author><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Struthers Parkinson's Center, Golden Valley, Minnesota</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Freeman, Alan" sort="Freeman, Alan" uniqKey="Freeman A" first="Alan" last="Freeman">Alan Freeman</name>
<affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Emory University, Atlanta, Georgia</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</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 wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kefi, Mounir" sort="Kefi, Mounir" uniqKey="Kefi M" first="Mounir" last="Kefi">Mounir Kefi</name>
<affiliation wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zouari, Mourad" sort="Zouari, Mourad" uniqKey="Zouari M" first="Mourad" last="Zouari">Mourad Zouari</name>
<affiliation wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Tunisie</country>
<wicri:regionArea>Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis</wicri:regionArea>
<wicri:noRegion>Tunis</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Middleton, Lefkos" sort="Middleton, Lefkos" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name>
<affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals, Greenford</wicri:regionArea>
<wicri:noRegion>Greenford</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Neurology, Newcastle General Hospital, Newcastle‐upon‐Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle‐upon‐Tyne</wicri:noRegion>
</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 wicri:level="2"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Hentati, Faycal" sort="Hentati, Faycal" uniqKey="Hentati F" first="Faycal" last="Hentati">Faycal Hentati</name>
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<series><title level="j">Movement Disorders</title>
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<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>
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<PubMed><TEI><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>
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<wicri:regionArea>Department of Public Health and Primary Care, University of Cambridge, Cambridge</wicri:regionArea>
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<author><name sortKey="Gibson, Rachel A" sort="Gibson, Rachel A" uniqKey="Gibson R" first="Rachel A" last="Gibson">Rachel A. Gibson</name>
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<author><name sortKey="Warren, Liling" sort="Warren, Liling" uniqKey="Warren L" first="Liling" last="Warren">Liling Warren</name>
</author>
<author><name sortKey="Amouri, Rim" sort="Amouri, Rim" uniqKey="Amouri R" first="Rim" last="Amouri">Rim Amouri</name>
</author>
<author><name sortKey="Lyons, Kelly" sort="Lyons, Kelly" uniqKey="Lyons K" first="Kelly" last="Lyons">Kelly Lyons</name>
</author>
<author><name sortKey="Wielinski, Catherine" sort="Wielinski, Catherine" uniqKey="Wielinski C" first="Catherine" last="Wielinski">Catherine Wielinski</name>
</author>
<author><name sortKey="Hunter, Christine" sort="Hunter, Christine" uniqKey="Hunter C" first="Christine" last="Hunter">Christine Hunter</name>
</author>
<author><name sortKey="Swartz, Jina E" sort="Swartz, Jina E" uniqKey="Swartz J" first="Jina E" last="Swartz">Jina E. Swartz</name>
</author>
<author><name sortKey="Elango, Ramu" sort="Elango, Ramu" uniqKey="Elango R" first="Ramu" last="Elango">Ramu Elango</name>
</author>
<author><name sortKey="Akkari, P Anthony" sort="Akkari, P Anthony" uniqKey="Akkari P" first="P Anthony" last="Akkari">P Anthony Akkari</name>
</author>
<author><name sortKey="Leppert, David" sort="Leppert, David" uniqKey="Leppert D" first="David" last="Leppert">David Leppert</name>
</author>
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<author><name sortKey="Reeves, Kevin H" sort="Reeves, Kevin H" uniqKey="Reeves K" first="Kevin H" last="Reeves">Kevin H. Reeves</name>
</author>
<author><name sortKey="Thomas, Siwan" sort="Thomas, Siwan" uniqKey="Thomas S" first="Siwan" last="Thomas">Siwan Thomas</name>
</author>
<author><name sortKey="Ragone, Leigh" sort="Ragone, Leigh" uniqKey="Ragone L" first="Leigh" last="Ragone">Leigh Ragone</name>
</author>
<author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name>
</author>
<author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation><country>États-Unis</country>
<placeName><settlement type="city">Houston</settlement>
<region type="state">Texas</region>
</placeName>
<orgName type="university" n="3">Baylor College of Medicine</orgName>
</affiliation>
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</author>
<author><name sortKey="Freeman, Alan" sort="Freeman, Alan" uniqKey="Freeman A" first="Alan" last="Freeman">Alan Freeman</name>
</author>
<author><name sortKey="Gouider Khouja, Neziha" sort="Gouider Khouja, Neziha" uniqKey="Gouider Khouja N" first="Neziha" last="Gouider-Khouja">Neziha Gouider-Khouja</name>
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<region type="country">Angleterre</region>
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<author><name sortKey="Gibson, Rachel A" sort="Gibson, Rachel A" uniqKey="Gibson R" first="Rachel A" last="Gibson">Rachel A. Gibson</name>
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<author><name sortKey="Warren, Liling" sort="Warren, Liling" uniqKey="Warren L" first="Liling" last="Warren">Liling Warren</name>
</author>
<author><name sortKey="Amouri, Rim" sort="Amouri, Rim" uniqKey="Amouri R" first="Rim" last="Amouri">Rim Amouri</name>
</author>
<author><name sortKey="Lyons, Kelly" sort="Lyons, Kelly" uniqKey="Lyons K" first="Kelly" last="Lyons">Kelly Lyons</name>
</author>
<author><name sortKey="Wielinski, Catherine" sort="Wielinski, Catherine" uniqKey="Wielinski C" first="Catherine" last="Wielinski">Catherine Wielinski</name>
</author>
<author><name sortKey="Hunter, Christine" sort="Hunter, Christine" uniqKey="Hunter C" first="Christine" last="Hunter">Christine Hunter</name>
</author>
<author><name sortKey="Swartz, Jina E" sort="Swartz, Jina E" uniqKey="Swartz J" first="Jina E" last="Swartz">Jina E. Swartz</name>
</author>
<author><name sortKey="Elango, Ramu" sort="Elango, Ramu" uniqKey="Elango R" first="Ramu" last="Elango">Ramu Elango</name>
</author>
<author><name sortKey="Akkari, P Anthony" sort="Akkari, P Anthony" uniqKey="Akkari P" first="P Anthony" last="Akkari">P Anthony Akkari</name>
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<author><name sortKey="Leppert, David" sort="Leppert, David" uniqKey="Leppert D" first="David" last="Leppert">David Leppert</name>
</author>
<author><name sortKey="Surh, Linda" sort="Surh, Linda" uniqKey="Surh L" first="Linda" last="Surh">Linda Surh</name>
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<author><name sortKey="Reeves, Kevin H" sort="Reeves, Kevin H" uniqKey="Reeves K" first="Kevin H" last="Reeves">Kevin H. Reeves</name>
</author>
<author><name sortKey="Thomas, Siwan" sort="Thomas, Siwan" uniqKey="Thomas S" first="Siwan" last="Thomas">Siwan Thomas</name>
</author>
<author><name sortKey="Ragone, Leigh" sort="Ragone, Leigh" uniqKey="Ragone L" first="Leigh" last="Ragone">Leigh Ragone</name>
</author>
<author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name>
</author>
<author><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name>
</author>
<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation><country>États-Unis</country>
<placeName><settlement type="city">Houston</settlement>
<region type="state">Texas</region>
</placeName>
<orgName type="university" n="3">Baylor College of Medicine</orgName>
</affiliation>
</author>
<author><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name>
</author>
<author><name sortKey="Freeman, Alan" sort="Freeman, Alan" uniqKey="Freeman A" first="Alan" last="Freeman">Alan Freeman</name>
</author>
<author><name sortKey="Gouider Khouja, Neziha" sort="Gouider Khouja, Neziha" uniqKey="Gouider Khouja N" first="Neziha" last="Gouider-Khouja">Neziha Gouider-Khouja</name>
</author>
<author><name sortKey="Kefi, Mounir" sort="Kefi, Mounir" uniqKey="Kefi M" first="Mounir" last="Kefi">Mounir Kefi</name>
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</author>
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</author>
<author><name sortKey="El Euch Fayeche, Ghada" sort="El Euch Fayeche, Ghada" uniqKey="El Euch Fayeche G" first="Ghada" last="El Euch-Fayeche">Ghada El Euch-Fayeche</name>
</author>
<author><name sortKey="Middleton, Lefkos" sort="Middleton, Lefkos" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name>
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<author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray L" last="Watts">Ray L. Watts</name>
</author>
<author><name sortKey="Hentati, Faycal" sort="Hentati, Faycal" uniqKey="Hentati F" first="Faycal" last="Hentati">Faycal Hentati</name>
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<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
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<imprint><date when="2007" type="published">2007</date>
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<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Cross-Cultural Comparison</term>
<term>DNA Mutational Analysis</term>
<term>European Continental Ancestry Group</term>
<term>Family Health</term>
<term>Female</term>
<term>Genetic Testing (methods)</term>
<term>Genotype</term>
<term>Glycine (genetics)</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Mutation (genetics)</term>
<term>North America (epidemiology)</term>
<term>North America (ethnology)</term>
<term>Parkinson Disease (epidemiology)</term>
<term>Parkinson Disease (genetics)</term>
<term>Protein-Serine-Threonine Kinases (genetics)</term>
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<term>Tunisia (epidemiology)</term>
<term>Tunisia (ethnology)</term>
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<term>Family Health</term>
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<term>Genotype</term>
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<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.</div>
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