Analysis of Parkinson's disease brain–derived DNA for alpha-synuclein coding somatic mutations
Identifieur interne : 003F58 ( Ncbi/Checkpoint ); précédent : 003F57; suivant : 003F59Analysis of Parkinson's disease brain–derived DNA for alpha-synuclein coding somatic mutations
Auteurs : Christos Proukakis [Royaume-Uni] ; Maryiam Shoaee [Royaume-Uni] ; James Morris [Royaume-Uni] ; Timothy Brier [Royaume-Uni] ; Eleanna Kara [Royaume-Uni] ; Una-Marie Sheerin [Royaume-Uni] ; Gavin Charlesworth [Royaume-Uni] ; Eduardo Tolosa [Espagne] ; Henry Houlden [Royaume-Uni] ; Nicholas W. Wood [Royaume-Uni] ; Anthony H. Schapira [Royaume-Uni]Source :
- Movement Disorders [ 0885-3185 ] ; 2014.
English descriptors
- KwdEn :
- Brain (metabolism), Brain (pathology), DNA (metabolism), Female, Genetic Predisposition to Disease (genetics), Genetic Testing, Humans, Lewy Body Disease (complications), Lewy Body Disease (genetics), Lewy Body Disease (pathology), Male, Mutation (genetics), Parkinson Disease (complications), Parkinson Disease (genetics), Parkinson Disease (pathology), alpha-Synuclein (genetics), alpha-Synuclein (metabolism).
- MESH :
- chemical , genetics : alpha-Synuclein.
- chemical , metabolism : DNA, alpha-Synuclein.
- complications : Lewy Body Disease, Parkinson Disease.
- genetics : Genetic Predisposition to Disease, Lewy Body Disease, Mutation, Parkinson Disease.
- metabolism : Brain.
- pathology : Brain, Lewy Body Disease, Parkinson Disease.
- Female, Genetic Testing, Humans, Male.
Abstract
Although alpha-synuclein (SNCA) is crucial to the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), mutations in the gene appear to be rare. We have recently hypothesized that somatic mutations in early development could contribute to PD.
Expanding on our recent negative small study, we used high-resolution melting (HRM) analysis to screen
We did not detect any evidence of somatic coding mutations. Three cases were heterozygous for known silent polymorphisms. The protocol we used was sensitive enough to detect 5% to 10% mutant DNA.
Using DNA predominantly from cerebellum, but also from frontal cortex and substantia nigra (n = 20 each), we have not detected any somatic coding
Url:
DOI: 10.1002/mds.25883
PubMed: 24752924
PubMed Central: 4190821
Affiliations:
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<series><title level="j">Movement Disorders</title>
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<term>Female</term>
<term>Genetic Predisposition to Disease (genetics)</term>
<term>Genetic Testing</term>
<term>Humans</term>
<term>Lewy Body Disease (complications)</term>
<term>Lewy Body Disease (genetics)</term>
<term>Lewy Body Disease (pathology)</term>
<term>Male</term>
<term>Mutation (genetics)</term>
<term>Parkinson Disease (complications)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (pathology)</term>
<term>alpha-Synuclein (genetics)</term>
<term>alpha-Synuclein (metabolism)</term>
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<term>alpha-Synuclein</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Lewy Body Disease</term>
<term>Parkinson Disease</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genetic Predisposition to Disease</term>
<term>Lewy Body Disease</term>
<term>Mutation</term>
<term>Parkinson Disease</term>
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<term>Parkinson Disease</term>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Although alpha-synuclein (SNCA) is crucial to the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), mutations in the gene appear to be rare. We have recently hypothesized that somatic mutations in early development could contribute to PD.</p>
</sec>
<sec><title>Methods</title>
<p>Expanding on our recent negative small study, we used high-resolution melting (HRM) analysis to screen <italic>SNCA</italic>
coding exons for somatic point mutations in DNA from 539 PD and DLB cerebellar samples, with two additional regions (frontal cortex, substantia nigra) for 20 PD cases. We used artificial mosaics to determine sensitivity where possible.</p>
</sec>
<sec><title>Results</title>
<p>We did not detect any evidence of somatic coding mutations. Three cases were heterozygous for known silent polymorphisms. The protocol we used was sensitive enough to detect 5% to 10% mutant DNA.</p>
</sec>
<sec><title>Conclusion</title>
<p>Using DNA predominantly from cerebellum, but also from frontal cortex and substantia nigra (n = 20 each), we have not detected any somatic coding <italic>SNCA</italic>
point mutations. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</p>
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</analytic>
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</author>
<author><name sortKey="Boulkroun, S" uniqKey="Boulkroun S">S Boulkroun</name>
</author>
<author><name sortKey="Osswald, A" uniqKey="Osswald A">A Osswald</name>
</author>
</analytic>
</biblStruct>
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</author>
<author><name sortKey="Goh, G" uniqKey="Goh G">G Goh</name>
</author>
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<affiliations><list><country><li>Espagne</li>
<li>Royaume-Uni</li>
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<tree><country name="Royaume-Uni"><noRegion><name sortKey="Proukakis, Christos" sort="Proukakis, Christos" uniqKey="Proukakis C" first="Christos" last="Proukakis">Christos Proukakis</name>
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<name sortKey="Brier, Timothy" sort="Brier, Timothy" uniqKey="Brier T" first="Timothy" last="Brier">Timothy Brier</name>
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<name sortKey="Houlden, Henry" sort="Houlden, Henry" uniqKey="Houlden H" first="Henry" last="Houlden">Henry Houlden</name>
<name sortKey="Kara, Eleanna" sort="Kara, Eleanna" uniqKey="Kara E" first="Eleanna" last="Kara">Eleanna Kara</name>
<name sortKey="Morris, James" sort="Morris, James" uniqKey="Morris J" first="James" last="Morris">James Morris</name>
<name sortKey="Schapira, Anthony H" sort="Schapira, Anthony H" uniqKey="Schapira A" first="Anthony H" last="Schapira">Anthony H. Schapira</name>
<name sortKey="Sheerin, Una Marie" sort="Sheerin, Una Marie" uniqKey="Sheerin U" first="Una-Marie" last="Sheerin">Una-Marie Sheerin</name>
<name sortKey="Shoaee, Maryiam" sort="Shoaee, Maryiam" uniqKey="Shoaee M" first="Maryiam" last="Shoaee">Maryiam Shoaee</name>
<name sortKey="Wood, Nicholas W" sort="Wood, Nicholas W" uniqKey="Wood N" first="Nicholas W" last="Wood">Nicholas W. Wood</name>
</country>
<country name="Espagne"><noRegion><name sortKey="Tolosa, Eduardo" sort="Tolosa, Eduardo" uniqKey="Tolosa E" first="Eduardo" last="Tolosa">Eduardo Tolosa</name>
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</tree>
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