MovDisordV3, Main, Exploration, bibRecord, 002D31

Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements

Identifieur interne : 002D31 ( Main/Exploration ); précédent : 002D30; suivant : 002D32

Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements

Auteurs : Oronzo Scarciolla [Italie] ; Francesco Brancati [Italie] ; Enza Maria Valente [Italie] ; Alessandro Ferraris [Italie] ; Maria Vittoria De Angelis [Italie] ; Stefano Valbonesi [Italie] ; Barbara Garavaglia [Italie] ; Antonino Uncini [Italie] ; Giandomenico Palka [Italie] ; Liborio Stuppia [Italie] ; Bruno Dallapiccola [Italie]

Source :

Movement Disorders [ 0885-3185 ] ; 2007-11-15.

RBID : ISTEX:942C58D5A57940D9B72ED98953BD2851C4892263

Descripteurs français

Pascal (Inist)
- Amplification, Maladie de Parkinson, Mesure simultanée, Parkinsonisme, Pathologie du système nerveux, Réarrangement génique.

English descriptors

KwdEn :
- Adolescent, Adult, Age of Onset, Amplification, Gene Rearrangement, Gene rearrangement, Genes, Dominant, Genes, Recessive, Genetic Testing (methods), Humans, Intracellular Signaling Peptides and Proteins (genetics), MLPA, Middle Aged, Nervous system diseases, Nucleic Acid Amplification Techniques (methods), Oncogene Proteins (genetics), Parkinson Disease (genetics), Parkinson disease, Parkinson's disease, Parkinsonism, Protein Kinases (genetics), Protein-Serine-Threonine Kinases (genetics), Simultaneous measurement, Ubiquitin-Protein Ligases (genetics), alpha-Synuclein (genetics), early onset parkinsonism, genomic rearrangements.
MESH :
- chemical , genetics : Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Protein Kinases, Protein-Serine-Threonine Kinases, Ubiquitin-Protein Ligases, alpha-Synuclein.
- genetics : Parkinson Disease.
- methods : Genetic Testing, Nucleic Acid Amplification Techniques.
- Adolescent, Adult, Age of Onset, Gene Rearrangement, Genes, Dominant, Genes, Recessive, Humans, Middle Aged.

Abstract

Parkinson's disease (PD) is a common disorder caused by degeneration of dopaminergic neurons in the substantia nigra and other brain areas. Mutations in several genes have been associated with both autosomal dominant PD and recessive early onset Parkinsonism (EOP). Genomic rearrangements such as deletions or multiplications of one or more exons represent a common mutational mechanism for most of these genes and are not detectable with routine mutation screening techniques. MLPA (Multiplex Ligation‐dependent Probe Amplification), is a cheap, simple, rapid, and sensitive tool to detect exon dosage alterations and specific point mutations in selected genes. We tested the recently developed PD‐MLPA assay by using 13 positive control samples carrying known mutations in SNCA, LRRK2, Parkin, PINK1, and DJ‐1 genes. We then applied this technique to screen 16 EOP patients who were then cross‐tested by quantitative PCR (qPCR). All the mutations present in the positive control samples were clearly detected by MLPA. Moreover, three novel Parkin rearrangements were identified among EOP patients and confirmed by qPCR. Only two samples generated false positive duplications of LRRK2 exon 1 and UCH‐L1 exon 9, respectively. These results show that PD‐MLPA assay can simultaneously and effectively detect rearrangements in most PD genes (SNCA, Parkin, PINK1, and DJ‐1) as well as the LRRK2 G2019S common mutation. Thus, the use of this novel platform can improve the analysis of such mutations, facilitating comprehensive genetic testing in PD and EOP. © 2007 Movement Disorder Society

Url:

https://api.istex.fr/document/942C58D5A57940D9B72ED98953BD2851C4892263/fulltext/pdf

DOI: 10.1002/mds.21532

Affiliations:

Le document en format XML

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<term>Adult</term>
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<term>Amplification</term>
<term>Gene Rearrangement</term>
<term>Gene rearrangement</term>
<term>Genes, Dominant</term>
<term>Genes, Recessive</term>
<term>Genetic Testing (methods)</term>
<term>Humans</term>
<term>Intracellular Signaling Peptides and Proteins (genetics)</term>
<term>MLPA</term>
<term>Middle Aged</term>
<term>Nervous system diseases</term>
<term>Nucleic Acid Amplification Techniques (methods)</term>
<term>Oncogene Proteins (genetics)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson disease</term>
<term>Parkinson's disease</term>
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<term>Simultaneous measurement</term>
<term>Ubiquitin-Protein Ligases (genetics)</term>
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<term>genomic rearrangements</term>
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<front><div type="abstract" xml:lang="en">Parkinson's disease (PD) is a common disorder caused by degeneration of dopaminergic neurons in the substantia nigra and other brain areas. Mutations in several genes have been associated with both autosomal dominant PD and recessive early onset Parkinsonism (EOP). Genomic rearrangements such as deletions or multiplications of one or more exons represent a common mutational mechanism for most of these genes and are not detectable with routine mutation screening techniques. MLPA (Multiplex Ligation‐dependent Probe Amplification), is a cheap, simple, rapid, and sensitive tool to detect exon dosage alterations and specific point mutations in selected genes. We tested the recently developed PD‐MLPA assay by using 13 positive control samples carrying known mutations in SNCA, LRRK2, Parkin, PINK1, and DJ‐1 genes. We then applied this technique to screen 16 EOP patients who were then cross‐tested by quantitative PCR (qPCR). All the mutations present in the positive control samples were clearly detected by MLPA. Moreover, three novel Parkin rearrangements were identified among EOP patients and confirmed by qPCR. Only two samples generated false positive duplications of LRRK2 exon 1 and UCH‐L1 exon 9, respectively. These results show that PD‐MLPA assay can simultaneously and effectively detect rearrangements in most PD genes (SNCA, Parkin, PINK1, and DJ‐1) as well as the LRRK2 G2019S common mutation. Thus, the use of this novel platform can improve the analysis of such mutations, facilitating comprehensive genetic testing in PD and EOP. © 2007 Movement Disorder Society</div>
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<name sortKey="Stuppia, Liborio" sort="Stuppia, Liborio" uniqKey="Stuppia L" first="Liborio" last="Stuppia">Liborio Stuppia</name>
<name sortKey="Stuppia, Liborio" sort="Stuppia, Liborio" uniqKey="Stuppia L" first="Liborio" last="Stuppia">Liborio Stuppia</name>
<name sortKey="Stuppia, Liborio" sort="Stuppia, Liborio" uniqKey="Stuppia L" first="Liborio" last="Stuppia">Liborio Stuppia</name>
<name sortKey="Uncini, Antonino" sort="Uncini, Antonino" uniqKey="Uncini A" first="Antonino" last="Uncini">Antonino Uncini</name>
<name sortKey="Uncini, Antonino" sort="Uncini, Antonino" uniqKey="Uncini A" first="Antonino" last="Uncini">Antonino Uncini</name>
<name sortKey="Valbonesi, Stefano" sort="Valbonesi, Stefano" uniqKey="Valbonesi S" first="Stefano" last="Valbonesi">Stefano Valbonesi</name>
<name sortKey="Valbonesi, Stefano" sort="Valbonesi, Stefano" uniqKey="Valbonesi S" first="Stefano" last="Valbonesi">Stefano Valbonesi</name>
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<name sortKey="Valente, Enza Maria" sort="Valente, Enza Maria" uniqKey="Valente E" first="Enza Maria" last="Valente">Enza Maria Valente</name>
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Movement Disorders (revue)

Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements

Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements

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	Movement Disorders (revue)
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