MovDisordV3, Main, Exploration, bibRecord, 000664

Analysis of Parkinson's disease brain–derived DNA for alpha-synuclein coding somatic mutations

Identifieur interne : 000664 ( Main/Exploration ); précédent : 000663; suivant : 000665

Analysis 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.

RBID : PMC:4190821

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

Background

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.

Methods

Expanding on our recent negative small study, we used high-resolution melting (HRM) analysis to screen SNCA 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.

Results

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.

Conclusion

Using DNA predominantly from cerebellum, but also from frontal cortex and substantia nigra (n = 20 each), we have not detected any somatic coding SNCA point mutations. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190821

DOI: 10.1002/mds.25883
PubMed: 24752924
PubMed Central: 4190821

Affiliations:

Le document en format XML

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<series><title level="j">Movement Disorders</title>
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<term>alpha-Synuclein</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>
</sec>
</div>
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Movement Disorders (revue)

Analysis of Parkinson's disease brain–derived DNA for alpha-synuclein coding somatic mutations

Analysis of Parkinson's disease brain–derived DNA for alpha-synuclein coding somatic mutations

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	Movement Disorders (revue)
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