A comparative study of LRRK2, PINK1 and genetically undefined familial Parkinson's disease
Identifieur interne : 000485 ( Main/Exploration ); précédent : 000484; suivant : 000486A comparative study of LRRK2, PINK1 and genetically undefined familial Parkinson's disease
Auteurs : Kenya Nishioka [États-Unis] ; Mounir Kefi [Tunisie] ; Barbara Jasinska-Myga [États-Unis, Pologne] ; Christian Wider [États-Unis] ; Carles Vilari O-Güell [États-Unis] ; Owen A. Ross [États-Unis] ; Michael G. Heckman [États-Unis] ; Lefkos T. Middleton [Royaume-Uni] ; Lianna Ishihara-Paul [Royaume-Uni] ; Rachel A. Gibson [Royaume-Uni] ; Rim Amouri [Tunisie] ; Samia Ben Yahmed [Tunisie] ; Samia Ben Sassi [Tunisie] ; Mourad Zouari [Tunisie] ; Ghada El Euch [Tunisie] ; Matthew J. Farrer [États-Unis] ; Faycal Hentati [Tunisie]Source :
- Journal of Neurology, Neurosurgery & Psychiatry [ 0022-3050 ] ; 2010-04.
Abstract
Genetic classification of Parkinson's disease (PD) subtypes may become the preferred diagnostic tool for neurologists. Herein we compare clinical features from a large cohort of patients with familial PD of unknown aetiology or attributable to distinct genetic forms. Comprehensive neurological examinations were performed in 231 familial PD patients from Tunisia. Analysis was previously performed to screen for mutations in leucine rich repeat kinase 2 (LRRK2), PTEN induced kinase 1 (PINK1) and parkin (PRKN). Clinical features were compared between patients with genetically undefined PD (n=107) and those with LRRK2 (n=73) and PINK1 (n=42) mutations using regression analyses adjusted for gender, age of onset and disease duration. PRKN cases (n=9) were too few for meaningful statistical analysis. In comparison with genetically undefined patients, LRRK2 mutation carriers had more severe motor symptoms (median Unified Parkinson's Disease Rating Scale scores ∼1.6 times higher, p<0.001), a higher rate of dyskinesia (OR 4.21, p=0.002) and use of dopamine agonists (OR 3.64, p<0.001), and less postural tremor (OR 0.21, p<0.001). PINK1 mutation carriers presented an increased rate of drug induced dyskinesia (OR 3.81, p=0.007) and a lower rate of postural tremor (OR 0.16, p<0.001) than genetically undefined patients. As expected, PINK1 patients had younger ages and ages at disease onset, and a longer disease duration compared with LRRK2 mutation carriers and genetically undefined patients. Clinical differences between LRRK2, PINK1 and genetically undefined familial PD appear more pronounced than previously appreciated, and may prove useful in clinical practice. As future therapies are targeted to specific protein abnormalities, identifying the genetic causes and associated clinical and pathological features will determine diagnosis, preventative medicine and drug intervention strategies.
Url:
DOI: 10.1136/jnnp.2009.185231
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>A comparative study of LRRK2, PINK1 and genetically undefined familial Parkinson's disease</title><author><name sortKey="Nishioka, Kenya" sort="Nishioka, Kenya" uniqKey="Nishioka K" first="Kenya" last="Nishioka">Kenya Nishioka</name></author><author><name sortKey="Kefi, Mounir" sort="Kefi, Mounir" uniqKey="Kefi M" first="Mounir" last="Kefi">Mounir Kefi</name></author><author><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name></author><author><name sortKey="Wider, Christian" sort="Wider, Christian" uniqKey="Wider C" first="Christian" last="Wider">Christian Wider</name></author><author><name sortKey="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A" last="Ross">Owen A. Ross</name></author><author><name sortKey="Heckman, Michael G" sort="Heckman, Michael G" uniqKey="Heckman M" first="Michael G" last="Heckman">Michael G. Heckman</name></author><author><name sortKey="Middleton, Lefkos T" sort="Middleton, Lefkos T" uniqKey="Middleton L" first="Lefkos T" last="Middleton">Lefkos T. Middleton</name></author><author><name sortKey="Ishihara Paul, Lianna" sort="Ishihara Paul, Lianna" uniqKey="Ishihara Paul L" first="Lianna" last="Ishihara-Paul">Lianna Ishihara-Paul</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="Amouri, Rim" sort="Amouri, Rim" uniqKey="Amouri R" first="Rim" last="Amouri">Rim Amouri</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="Ben Sassi, Samia" sort="Ben Sassi, Samia" uniqKey="Ben Sassi S" first="Samia" last="Ben Sassi">Samia Ben Sassi</name></author><author><name sortKey="Zouari, Mourad" sort="Zouari, Mourad" uniqKey="Zouari M" first="Mourad" last="Zouari">Mourad Zouari</name></author><author><name sortKey="El Euch, Ghada" sort="El Euch, Ghada" uniqKey="El Euch G" first="Ghada" last="El Euch">Ghada El Euch</name></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. Farrer</name></author><author><name sortKey="Hentati, Faycal" sort="Hentati, Faycal" uniqKey="Hentati F" first="Faycal" last="Hentati">Faycal Hentati</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:BE8BFE0EC934CF35A89D5E71960AE3D6BBE9A8CF</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1136/jnnp.2009.185231</idno><idno type="url">https://api.istex.fr/document/BE8BFE0EC934CF35A89D5E71960AE3D6BBE9A8CF/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002C84</idno><idno type="wicri:Area/Main/Curation">002911</idno><idno type="wicri:Area/Main/Exploration">000485</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">A comparative study of LRRK2, PINK1 and genetically undefined familial Parkinson's disease</title><author><name sortKey="Nishioka, Kenya" sort="Nishioka, Kenya" uniqKey="Nishioka K" first="Kenya" last="Nishioka">Kenya Nishioka</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</wicri:regionArea><placeName><region type="state">Floride</region></placeName></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="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Pologne</country><wicri:regionArea>Department of Neurology, Ageing, Degenerative and Cerebrovascular Disorders, Medical University of Silesia, Katowice</wicri:regionArea><wicri:noRegion>Katowice</wicri:noRegion></affiliation></author><author><name sortKey="Wider, Christian" sort="Wider, Christian" uniqKey="Wider C" first="Christian" last="Wider">Christian Wider</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A" last="Ross">Owen A. Ross</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Heckman, Michael G" sort="Heckman, Michael G" uniqKey="Heckman M" first="Michael G" last="Heckman">Michael G. Heckman</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biostatistics Unit, Mayo Clinic, Jacksonville, Florida</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Middleton, Lefkos T" sort="Middleton, Lefkos T" uniqKey="Middleton L" first="Lefkos T" last="Middleton">Lefkos T. Middleton</name><affiliation wicri:level="3"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Neuroscience, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Ishihara Paul, Lianna" sort="Ishihara Paul, Lianna" uniqKey="Ishihara Paul L" first="Lianna" last="Ishihara-Paul">Lianna Ishihara-Paul</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Research and Development, GlaxoSmithKline Pharmaceuticals Ltd, Harlow</wicri:regionArea><wicri:noRegion>Harlow</wicri:noRegion></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 Ltd, Harlow</wicri:regionArea><wicri:noRegion>Harlow</wicri:noRegion></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="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="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="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="El Euch, Ghada" sort="El Euch, Ghada" uniqKey="El Euch G" first="Ghada" last="El Euch">Ghada El Euch</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="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. Farrer</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</wicri:regionArea><placeName><region type="state">Floride</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">Journal of Neurology, Neurosurgery & Psychiatry</title><title level="j" type="abbrev">J Neurol Neurosurg Psychiatry</title><idno type="ISSN">0022-3050</idno><idno type="eISSN">1468-330X</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2010-04">2010-04</date><biblScope unit="volume">81</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="391">391</biblScope></imprint><idno type="ISSN">0022-3050</idno></series><idno type="istex">BE8BFE0EC934CF35A89D5E71960AE3D6BBE9A8CF</idno><idno type="DOI">10.1136/jnnp.2009.185231</idno><idno type="href">jnnp-81-391.pdf</idno><idno type="ArticleID">jnnp185231</idno><idno type="PMID">19726410</idno><idno type="local">jnnp;81/4/391</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3050</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Genetic classification of Parkinson's disease (PD) subtypes may become the preferred diagnostic tool for neurologists. Herein we compare clinical features from a large cohort of patients with familial PD of unknown aetiology or attributable to distinct genetic forms. Comprehensive neurological examinations were performed in 231 familial PD patients from Tunisia. Analysis was previously performed to screen for mutations in leucine rich repeat kinase 2 (LRRK2), PTEN induced kinase 1 (PINK1) and parkin (PRKN). Clinical features were compared between patients with genetically undefined PD (n=107) and those with LRRK2 (n=73) and PINK1 (n=42) mutations using regression analyses adjusted for gender, age of onset and disease duration. PRKN cases (n=9) were too few for meaningful statistical analysis. In comparison with genetically undefined patients, LRRK2 mutation carriers had more severe motor symptoms (median Unified Parkinson's Disease Rating Scale scores ∼1.6 times higher, p<0.001), a higher rate of dyskinesia (OR 4.21, p=0.002) and use of dopamine agonists (OR 3.64, p<0.001), and less postural tremor (OR 0.21, p<0.001). PINK1 mutation carriers presented an increased rate of drug induced dyskinesia (OR 3.81, p=0.007) and a lower rate of postural tremor (OR 0.16, p<0.001) than genetically undefined patients. As expected, PINK1 patients had younger ages and ages at disease onset, and a longer disease duration compared with LRRK2 mutation carriers and genetically undefined patients. Clinical differences between LRRK2, PINK1 and genetically undefined familial PD appear more pronounced than previously appreciated, and may prove useful in clinical practice. As future therapies are targeted to specific protein abnormalities, identifying the genetic causes and associated clinical and pathological features will determine diagnosis, preventative medicine and drug intervention strategies.</div></front></TEI><affiliations><list><country><li>Pologne</li><li>Royaume-Uni</li><li>Tunisie</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Floride</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement></list><tree><country name="États-Unis"><region name="Floride"><name sortKey="Nishioka, Kenya" sort="Nishioka, Kenya" uniqKey="Nishioka K" first="Kenya" last="Nishioka">Kenya Nishioka</name></region><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. Farrer</name><name sortKey="Heckman, Michael G" sort="Heckman, Michael G" uniqKey="Heckman M" first="Michael G" last="Heckman">Michael G. Heckman</name><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A" last="Ross">Owen A. Ross</name><name sortKey="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name><name sortKey="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name><name sortKey="Wider, Christian" sort="Wider, Christian" uniqKey="Wider C" first="Christian" last="Wider">Christian Wider</name></country><country name="Tunisie"><noRegion><name sortKey="Kefi, Mounir" sort="Kefi, Mounir" uniqKey="Kefi M" first="Mounir" last="Kefi">Mounir Kefi</name></noRegion><name sortKey="Amouri, Rim" sort="Amouri, Rim" uniqKey="Amouri R" first="Rim" last="Amouri">Rim Amouri</name><name sortKey="Ben Sassi, Samia" sort="Ben Sassi, Samia" uniqKey="Ben Sassi S" first="Samia" last="Ben Sassi">Samia Ben Sassi</name><name sortKey="Ben Yahmed, Samia" sort="Ben Yahmed, Samia" uniqKey="Ben Yahmed S" first="Samia" last="Ben Yahmed">Samia Ben Yahmed</name><name sortKey="El Euch, Ghada" sort="El Euch, Ghada" uniqKey="El Euch G" first="Ghada" last="El Euch">Ghada El Euch</name><name sortKey="Hentati, Faycal" sort="Hentati, Faycal" uniqKey="Hentati F" first="Faycal" last="Hentati">Faycal Hentati</name><name sortKey="Zouari, Mourad" sort="Zouari, Mourad" uniqKey="Zouari M" first="Mourad" last="Zouari">Mourad Zouari</name></country><country name="Pologne"><noRegion><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name></noRegion></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Middleton, Lefkos T" sort="Middleton, Lefkos T" uniqKey="Middleton L" first="Lefkos T" last="Middleton">Lefkos T. Middleton</name></region><name sortKey="Gibson, Rachel A" sort="Gibson, Rachel A" uniqKey="Gibson R" first="Rachel A" last="Gibson">Rachel A. Gibson</name><name sortKey="Ishihara Paul, Lianna" sort="Ishihara Paul, Lianna" uniqKey="Ishihara Paul L" first="Lianna" last="Ishihara-Paul">Lianna Ishihara-Paul</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000485 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000485 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:BE8BFE0EC934CF35A89D5E71960AE3D6BBE9A8CF
|texte= A comparative study of LRRK2, PINK1 and genetically undefined familial Parkinson's disease
}}
| This area was generated with Dilib version V0.6.23. |  |