Screening for Lrrk2 G2019S and clinical comparison of tunisian and North American caucasian Parkinson's disease families
Identifieur interne : 000E97 ( Main/Merge ); précédent : 000E96; suivant : 000E98Screening for Lrrk2 G2019S and clinical comparison of tunisian and North American caucasian Parkinson's disease families
Auteurs : Lianna Ishihara [Royaume-Uni] ; Rachel Gibson [Royaume-Uni] ; Liling Warren [États-Unis] ; Rim Amouri [Tunisie] ; Kelly Lyons [États-Unis] ; Catherine Wielinski [États-Unis] ; Christine Hunter [États-Unis] ; Jina Swartz [Royaume-Uni] ; Ramu Elango [Royaume-Uni] ; P Akkari [États-Unis] ; David Leppert [Royaume-Uni] ; Linda Surh [Royaume-Uni] ; Kevin 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 [Tunisie] ; Mounir Kefi [Tunisie] ; Mourad Zouari [Tunisie] ; Samia Ben [Tunisie] ; Samia Ben [Tunisie] ; Ghada El [Tunisie] ; Lefkos Middleton [Royaume-Uni] ; David Burn [Royaume-Uni] ; Ray Watts [États-Unis] ; Faycal Hentati [Tunisie]Source :
- Movement disorders [ 0885-3185 ] ; 2007.
Descripteurs français
- Pascal (Inist)
English descriptors
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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.
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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"><inist:fA14 i1="07"><s1>Department of Neurology, Baylor College of Medicine</s1><s2>Houston, Texas</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Swartz, Jina E" sort="Swartz, Jina E" uniqKey="Swartz J" first="Jina" last="Swartz">Jina Swartz</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><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"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Greenford</wicri:noRegion></affiliation></author><author><name sortKey="Akkari, P Anthony" sort="Akkari, P Anthony" uniqKey="Akkari P" first="P" last="Akkari">P Akkari</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park</s1><s2>Durham, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 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aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Greenford</wicri:noRegion></affiliation></author><author><name sortKey="Reeves, Kevin H" sort="Reeves, Kevin H" uniqKey="Reeves K" first="Kevin" last="Reeves">Kevin Reeves</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park</s1><s2>Durham, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><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"><inist:fA14 i1="03"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park</s1><s2>Durham, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="08"><s1>Department of Neurology, Juntendo University School of Medicine</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>16 aut.</sZ></inist:fA14><country>Japon</country><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"><inist:fA14 i1="05"><s1>Department of Neurology, University of Kansas Medical Center</s1><s2>Kansas City, Kansas</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="07"><s1>Department of Neurology, Baylor College of Medicine</s1><s2>Houston, Texas</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="06"><s1>Struthers Parkinson's Center</s1><s2>Golden Valley, Minnesota</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="09"><s1>Department of Neurology, Emory University</s1><s2>Atlanta, Georgia</s2><s3>USA</s3><sZ>20 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Gouider Khouja, Neziha" sort="Gouider Khouja, Neziha" uniqKey="Gouider Khouja N" first="Neziha" last="Gouider">Neziha Gouider</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, 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"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, 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"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, Tunis</wicri:noRegion></affiliation></author><author><name sortKey="Ben Sassi, Samia" sort="Ben Sassi, Samia" uniqKey="Ben Sassi S" first="Samia" last="Ben">Samia Ben</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, Tunis</wicri:noRegion></affiliation></author><author><name sortKey="Ben Yahmed, Samia" sort="Ben Yahmed, Samia" uniqKey="Ben Yahmed S" first="Samia" last="Ben">Samia Ben</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, Tunis</wicri:noRegion></affiliation></author><author><name sortKey="El Euch Fayeche, Ghada" sort="El Euch Fayeche, Ghada" uniqKey="El Euch Fayeche G" first="Ghada" last="El">Ghada El</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, 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"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Greenford</wicri:noRegion></affiliation></author><author><name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David" last="Burn">David Burn</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Department of Neurology, Newcastle General Hospital</s1><s2>Newcastle-upon-Tyne</s2><s3>GBR</s3><sZ>28 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Newcastle-upon-Tyne</wicri:noRegion></affiliation></author><author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray" last="Watts">Ray Watts</name><affiliation wicri:level="2"><inist:fA14 i1="11"><s1>Department of Neurology, University of Alabama at Birmingham</s1><s2>Birmingham, Alabama</s2><s3>USA</s3><sZ>29 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 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Ishihara</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Public Health and Primary Care, University of Cambridge</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Gibson, Rachel A" sort="Gibson, Rachel A" uniqKey="Gibson R" first="Rachel" last="Gibson">Rachel Gibson</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><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"><inist:fA14 i1="03"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park</s1><s2>Durham, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, 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"><inist:fA14 i1="05"><s1>Department of Neurology, University of Kansas Medical Center</s1><s2>Kansas City, Kansas</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="06"><s1>Struthers Parkinson's Center</s1><s2>Golden Valley, Minnesota</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="07"><s1>Department of Neurology, Baylor College of Medicine</s1><s2>Houston, Texas</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Swartz, Jina E" sort="Swartz, Jina E" uniqKey="Swartz J" first="Jina" last="Swartz">Jina Swartz</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><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"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Greenford</wicri:noRegion></affiliation></author><author><name sortKey="Akkari, P Anthony" sort="Akkari, P Anthony" uniqKey="Akkari P" first="P" last="Akkari">P Akkari</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park</s1><s2>Durham, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><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"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Greenford</wicri:noRegion></affiliation></author><author><name sortKey="Reeves, Kevin H" sort="Reeves, Kevin H" uniqKey="Reeves K" first="Kevin" last="Reeves">Kevin Reeves</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park</s1><s2>Durham, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><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"><inist:fA14 i1="03"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals, Research Triangle Park</s1><s2>Durham, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="08"><s1>Department of Neurology, Juntendo University School of Medicine</s1><s2>Tokyo</s2><s3>JPN</s3><sZ>16 aut.</sZ></inist:fA14><country>Japon</country><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"><inist:fA14 i1="05"><s1>Department of Neurology, University of Kansas Medical Center</s1><s2>Kansas City, Kansas</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="07"><s1>Department of Neurology, Baylor College of Medicine</s1><s2>Houston, Texas</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="06"><s1>Struthers Parkinson's Center</s1><s2>Golden Valley, Minnesota</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="09"><s1>Department of Neurology, Emory University</s1><s2>Atlanta, Georgia</s2><s3>USA</s3><sZ>20 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Gouider Khouja, Neziha" sort="Gouider Khouja, Neziha" uniqKey="Gouider Khouja N" first="Neziha" last="Gouider">Neziha Gouider</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, 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"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, 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"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, Tunis</wicri:noRegion></affiliation></author><author><name sortKey="Ben Sassi, Samia" sort="Ben Sassi, Samia" uniqKey="Ben Sassi S" first="Samia" last="Ben">Samia Ben</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, Tunis</wicri:noRegion></affiliation></author><author><name sortKey="Ben Yahmed, Samia" sort="Ben Yahmed, Samia" uniqKey="Ben Yahmed S" first="Samia" last="Ben">Samia Ben</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, Tunis</wicri:noRegion></affiliation></author><author><name sortKey="El Euch Fayeche, Ghada" sort="El Euch Fayeche, Ghada" uniqKey="El Euch Fayeche G" first="Ghada" last="El">Ghada El</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, 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"><inist:fA14 i1="02"><s1>Research and Development, GlaxoSmithKline Pharmaceuticals</s1><s2>Greenford</s2><s3>GBR</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Greenford</wicri:noRegion></affiliation></author><author><name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David" last="Burn">David Burn</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Department of Neurology, Newcastle General Hospital</s1><s2>Newcastle-upon-Tyne</s2><s3>GBR</s3><sZ>28 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Newcastle-upon-Tyne</wicri:noRegion></affiliation></author><author><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray" last="Watts">Ray Watts</name><affiliation wicri:level="2"><inist:fA14 i1="11"><s1>Department of Neurology, University of Alabama at Birmingham</s1><s2>Birmingham, Alabama</s2><s3>USA</s3><sZ>29 aut.</sZ></inist:fA14><country>États-Unis</country><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"><inist:fA14 i1="04"><s1>Service de Neurologie, Institut National de Neurologie</s1><s2>La Rabta, Tunis</s2><s3>TUN</s3><sZ>4 aut.</sZ><sZ>21 aut.</sZ><sZ>22 aut.</sZ><sZ>23 aut.</sZ><sZ>24 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>Tunisie</country><wicri:noRegion>La Rabta, Tunis</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>American</term><term>Comparative study</term><term>Medical screening</term><term>Nervous system diseases</term><term>North</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Système nerveux pathologie</term><term>Parkinson maladie</term><term>Dépistage</term><term>Etude comparative</term><term>Nord</term><term>Américain</term></keywords></textClass></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.</div></front></TEI><affiliations><list><country><li>Japon</li><li>Royaume-Uni</li><li>Tunisie</li><li>États-Unis</li></country><region><li>Alabama</li><li>Caroline du Nord</li><li>Géorgie (États-Unis)</li><li>Kansas</li><li>Minnesota</li><li>Texas</li></region><settlement><li>Houston</li><li>Tokyo</li></settlement><orgName><li>Baylor College of Medicine</li></orgName></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Ishihara, Lianna" sort="Ishihara, Lianna" uniqKey="Ishihara L" first="Lianna" last="Ishihara">Lianna Ishihara</name></noRegion><name sortKey="Burn, David J" sort="Burn, David J" uniqKey="Burn D" first="David" last="Burn">David Burn</name><name sortKey="Elango, Ramu" sort="Elango, Ramu" uniqKey="Elango R" first="Ramu" last="Elango">Ramu Elango</name><name sortKey="Gibson, Rachel A" sort="Gibson, Rachel A" uniqKey="Gibson R" first="Rachel" last="Gibson">Rachel Gibson</name><name sortKey="Leppert, David" sort="Leppert, David" uniqKey="Leppert D" first="David" last="Leppert">David Leppert</name><name sortKey="Middleton, Lefkos" sort="Middleton, Lefkos" uniqKey="Middleton L" first="Lefkos" last="Middleton">Lefkos Middleton</name><name sortKey="Surh, Linda" sort="Surh, Linda" uniqKey="Surh L" first="Linda" last="Surh">Linda Surh</name><name sortKey="Swartz, Jina E" sort="Swartz, Jina E" uniqKey="Swartz J" first="Jina" last="Swartz">Jina Swartz</name><name sortKey="Thomas, Siwan" sort="Thomas, Siwan" uniqKey="Thomas S" first="Siwan" last="Thomas">Siwan Thomas</name></country><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Warren, Liling" sort="Warren, Liling" uniqKey="Warren L" first="Liling" last="Warren">Liling Warren</name></region><name sortKey="Akkari, P Anthony" sort="Akkari, P Anthony" uniqKey="Akkari P" first="P" last="Akkari">P Akkari</name><name sortKey="Freeman, Alan" sort="Freeman, Alan" uniqKey="Freeman A" first="Alan" last="Freeman">Alan Freeman</name><name sortKey="Hunter, Christine" sort="Hunter, Christine" uniqKey="Hunter C" first="Christine" last="Hunter">Christine Hunter</name><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><name sortKey="Lyons, Kelly" sort="Lyons, Kelly" uniqKey="Lyons K" first="Kelly" last="Lyons">Kelly Lyons</name><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name><name sortKey="Ragone, Leigh" sort="Ragone, Leigh" uniqKey="Ragone L" first="Leigh" last="Ragone">Leigh Ragone</name><name sortKey="Reeves, Kevin H" sort="Reeves, Kevin H" uniqKey="Reeves K" first="Kevin" last="Reeves">Kevin Reeves</name><name sortKey="Watts, Ray L" sort="Watts, Ray L" uniqKey="Watts R" first="Ray" last="Watts">Ray Watts</name><name sortKey="Wielinski, Catherine" sort="Wielinski, Catherine" uniqKey="Wielinski C" first="Catherine" last="Wielinski">Catherine Wielinski</name></country><country name="Tunisie"><noRegion><name sortKey="Amouri, Rim" sort="Amouri, Rim" uniqKey="Amouri R" first="Rim" last="Amouri">Rim Amouri</name></noRegion><name sortKey="Ben Sassi, Samia" sort="Ben Sassi, Samia" uniqKey="Ben Sassi S" first="Samia" last="Ben">Samia Ben</name><name sortKey="Ben Yahmed, Samia" sort="Ben Yahmed, Samia" uniqKey="Ben Yahmed S" first="Samia" last="Ben">Samia Ben</name><name sortKey="El Euch Fayeche, Ghada" sort="El Euch Fayeche, Ghada" uniqKey="El Euch Fayeche G" first="Ghada" last="El">Ghada El</name><name sortKey="Gouider Khouja, Neziha" sort="Gouider Khouja, Neziha" uniqKey="Gouider Khouja N" first="Neziha" last="Gouider">Neziha Gouider</name><name sortKey="Hentati, Faycal" sort="Hentati, Faycal" uniqKey="Hentati F" first="Faycal" last="Hentati">Faycal Hentati</name><name sortKey="Kefi, Mounir" sort="Kefi, Mounir" uniqKey="Kefi M" first="Mounir" last="Kefi">Mounir Kefi</name><name sortKey="Zouari, Mourad" sort="Zouari, Mourad" uniqKey="Zouari M" first="Mourad" last="Zouari">Mourad Zouari</name></country><country name="Japon"><noRegion><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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