Rapid and reliable detection of exon rearrangements in various movement disorders genes by multiplex ligation-dependent probe amplification
Identifieur interne : 000608 ( PascalFrancis/Checkpoint ); précédent : 000607; suivant : 000609Rapid and reliable detection of exon rearrangements in various movement disorders genes by multiplex ligation-dependent probe amplification
Auteurs : Ana Djarmati [Allemagne] ; Miodrag Guzvic [Allemagne, Serbie] ; Anne Grünewald [Allemagne] ; Anthony E. Lang [Canada] ; Peter P. Pramstaller [Italie] ; David K. Simon [États-Unis] ; Angela M. Kaindl [Allemagne] ; Peter Vieregge [Allemagne] ; Anders O. H. Nygren [Pays-Bas] ; Christian Beetz [Allemagne] ; Katja Hedrich [Allemagne] ; Christine Klein [Allemagne]Source :
- Movement disorders [ 0885-3185 ] ; 2007.
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Abstract
Because of the occurrence of different types of mutations, comprehensive genetic testing for Parkinson's disease (PD), dopa-responsive dystonia (DRD), and myoclonus-dystonia (M-D) should include screening for small sequence changes and for large exonic rearrangements in disease-associated genes. In diagnostic and research settings, the latter is frequently omitted or performed by laborious and expensive quantitative real-time PCR (qPCR). Our study aimed to evaluate the utility of a novel method, multiplex ligation-dependent probe amplification (MLPA), in molecular diagnostics of movement disorders. We have analyzed, by MLPA, genomic DNA from 21 patients affected with PD, DRD, or M-D, in which the presence of exon rearrangement(s) (n = 20) or of a specific point mutation (detectable by MLPA, n = 1) had been established previously by qPCR or sequencing. In parallel, we have studied, in a blinded fashion, DNA from 49 patients with an unknown mutational status. Exon rearrangements were evident in 20 samples with previously established mutations; in the 21st sample the known specific point mutation was detected. We conclude that MLPA represents a reliable method for large-scale and cost-effective gene dosage screening of various movement disorders genes. This finding reaches far beyond a simple technical advancement and has two major implications: (1) By improving the availability of comprehensive genetic testing, it supports clinicians in the establishment of a genetically defined diagnosis; (2) By enabling gene dosage testing of several genes simultaneously, it significantly facilitates the mutational analysis of large patient and control populations and thereby constitutes the prerequisite for meaningful phenotype- genotype correlations.
Affiliations:
- Allemagne, Canada, Italie, Pays-Bas, Serbie, États-Unis
- Berlin, District de Dresde, Hollande-Septentrionale, Massachusetts, Saxe (Land)
- Amsterdam, Berlin, Dresde
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Lang</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Movement Disorders Centre, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P." last="Pramstaller">Peter P. Pramstaller</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Institute of Genetic Medicine, EURAC-Research</s1><s2>Bolzano-Bozen</s2><s3>ITA</s3><sZ>5 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Bolzano-Bozen</wicri:noRegion></affiliation></author><author><name sortKey="Simon, David K" sort="Simon, David K" uniqKey="Simon D" first="David K." last="Simon">David K. Simon</name><affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Kaindl, Angela M" sort="Kaindl, Angela M" uniqKey="Kaindl A" first="Angela M." last="Kaindl">Angela M. Kaindl</name><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Department of Pediatric Neurology, Charite University Medicine Berlin</s1><s2>Berlin</s2><s3>DEU</s3><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Department of Pediatric Neurology, University Hospital Dresden</s1><s2>Dresden</s2><s3>DEU</s3><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Saxe (Land)</region><region type="district" nuts="2">District de Dresde</region><settlement type="city">Dresde</settlement></placeName></affiliation></author><author><name sortKey="Vieregge, Peter" sort="Vieregge, Peter" uniqKey="Vieregge P" first="Peter" last="Vieregge">Peter Vieregge</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, University of Lübeck</s1><s2>Liibeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Liibeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>Liibeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Neurology, Hospital Lippe-Lemgo</s1><s2>Lemgo</s2><s3>DEU</s3><sZ>8 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Lemgo</wicri:noRegion><wicri:noRegion>Hospital Lippe-Lemgo</wicri:noRegion><wicri:noRegion>Lemgo</wicri:noRegion></affiliation></author><author><name sortKey="Nygren, Anders O H" sort="Nygren, Anders O H" uniqKey="Nygren A" first="Anders O. H." last="Nygren">Anders O. H. Nygren</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>MRC-Holland</s1><s2>Amsterdam</s2><s3>NLD</s3><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Beetz, Christian" sort="Beetz, Christian" uniqKey="Beetz C" first="Christian" last="Beetz">Christian Beetz</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Institut of Clinical Chemistry and Laboratory Diagnostics, University Hospital of the Friedrich Schiller University</s1><s2>Jena</s2><s3>DEU</s3><sZ>10 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>University Hospital of the Friedrich Schiller University</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Hedrich, Katja" sort="Hedrich, Katja" uniqKey="Hedrich K" first="Katja" last="Hedrich">Katja Hedrich</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, University of Lübeck</s1><s2>Liibeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Liibeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>Liibeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Human Genetics, University of Liibeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>University of Liibeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, University of Lübeck</s1><s2>Liibeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Liibeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>Liibeck</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">07-0491116</idno><date when="2007">2007</date><idno type="stanalyst">PASCAL 07-0491116 INIST</idno><idno type="RBID">Pascal:07-0491116</idno><idno type="wicri:Area/PascalFrancis/Corpus">000704</idno><idno type="wicri:Area/PascalFrancis/Curation">000616</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000608</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000608</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Rapid and reliable detection of exon rearrangements in various movement disorders genes by multiplex ligation-dependent probe amplification</title><author><name sortKey="Djarmati, Ana" sort="Djarmati, Ana" uniqKey="Djarmati A" first="Ana" last="Djarmati">Ana Djarmati</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, University of Lübeck</s1><s2>Liibeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Liibeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>Liibeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Human Genetics, University of Liibeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>University of Liibeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Guzvic, Miodrag" sort="Guzvic, Miodrag" uniqKey="Guzvic M" first="Miodrag" last="Guzvic">Miodrag Guzvic</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, University of Lübeck</s1><s2>Liibeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Liibeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>Liibeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Human Genetics, University of Liibeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>University of Liibeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Laboratory for Radiobiology and Molecular Genetics, Institute of Nuclear Sciences "Vinca"</s1><s2>Belgrade</s2><s3>SCG</s3><sZ>2 aut.</sZ></inist:fA14><country wicri:auto="SCG">Serbie</country><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Grunewald, Anne" sort="Grunewald, Anne" uniqKey="Grunewald A" first="Anne" last="Grünewald">Anne Grünewald</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, University of Lübeck</s1><s2>Liibeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Liibeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>Liibeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Human Genetics, University of Liibeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>University of Liibeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Movement Disorders Centre, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P." last="Pramstaller">Peter P. Pramstaller</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Institute of Genetic Medicine, EURAC-Research</s1><s2>Bolzano-Bozen</s2><s3>ITA</s3><sZ>5 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Bolzano-Bozen</wicri:noRegion></affiliation></author><author><name sortKey="Simon, David K" sort="Simon, David K" uniqKey="Simon D" first="David K." last="Simon">David K. Simon</name><affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Kaindl, Angela M" sort="Kaindl, Angela M" uniqKey="Kaindl A" first="Angela M." last="Kaindl">Angela M. Kaindl</name><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Department of Pediatric Neurology, Charite University Medicine Berlin</s1><s2>Berlin</s2><s3>DEU</s3><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Department of Pediatric Neurology, University Hospital Dresden</s1><s2>Dresden</s2><s3>DEU</s3><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Saxe (Land)</region><region type="district" nuts="2">District de Dresde</region><settlement type="city">Dresde</settlement></placeName></affiliation></author><author><name sortKey="Vieregge, Peter" sort="Vieregge, Peter" uniqKey="Vieregge P" first="Peter" last="Vieregge">Peter Vieregge</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, University of Lübeck</s1><s2>Liibeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Liibeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>Liibeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Neurology, Hospital Lippe-Lemgo</s1><s2>Lemgo</s2><s3>DEU</s3><sZ>8 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Lemgo</wicri:noRegion><wicri:noRegion>Hospital Lippe-Lemgo</wicri:noRegion><wicri:noRegion>Lemgo</wicri:noRegion></affiliation></author><author><name sortKey="Nygren, Anders O H" sort="Nygren, Anders O H" uniqKey="Nygren A" first="Anders O. H." last="Nygren">Anders O. H. Nygren</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>MRC-Holland</s1><s2>Amsterdam</s2><s3>NLD</s3><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Beetz, Christian" sort="Beetz, Christian" uniqKey="Beetz C" first="Christian" last="Beetz">Christian Beetz</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Institut of Clinical Chemistry and Laboratory Diagnostics, University Hospital of the Friedrich Schiller University</s1><s2>Jena</s2><s3>DEU</s3><sZ>10 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>University Hospital of the Friedrich Schiller University</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Hedrich, Katja" sort="Hedrich, Katja" uniqKey="Hedrich K" first="Katja" last="Hedrich">Katja Hedrich</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, University of Lübeck</s1><s2>Liibeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Liibeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>Liibeck</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Human Genetics, University of Liibeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>University of Liibeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, University of Lübeck</s1><s2>Liibeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Liibeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>Liibeck</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>Amplification</term><term>Dystonia</term><term>Exon</term><term>Gene rearrangement</term><term>Medical screening</term><term>Myoclonus</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Segawa disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Système nerveux pathologie</term><term>Parkinson maladie</term><term>Myoclonie</term><term>Dystonie</term><term>Dépistage</term><term>Exon</term><term>Réarrangement génique</term><term>Amplification</term><term>Segawa maladie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Because of the occurrence of different types of mutations, comprehensive genetic testing for Parkinson's disease (PD), dopa-responsive dystonia (DRD), and myoclonus-dystonia (M-D) should include screening for small sequence changes and for large exonic rearrangements in disease-associated genes. In diagnostic and research settings, the latter is frequently omitted or performed by laborious and expensive quantitative real-time PCR (qPCR). Our study aimed to evaluate the utility of a novel method, multiplex ligation-dependent probe amplification (MLPA), in molecular diagnostics of movement disorders. We have analyzed, by MLPA, genomic DNA from 21 patients affected with PD, DRD, or M-D, in which the presence of exon rearrangement(s) (n = 20) or of a specific point mutation (detectable by MLPA, n = 1) had been established previously by qPCR or sequencing. In parallel, we have studied, in a blinded fashion, DNA from 49 patients with an unknown mutational status. Exon rearrangements were evident in 20 samples with previously established mutations; in the 21st sample the known specific point mutation was detected. We conclude that MLPA represents a reliable method for large-scale and cost-effective gene dosage screening of various movement disorders genes. This finding reaches far beyond a simple technical advancement and has two major implications: (1) By improving the availability of comprehensive genetic testing, it supports clinicians in the establishment of a genetically defined diagnosis; (2) By enabling gene dosage testing of several genes simultaneously, it significantly facilitates the mutational analysis of large patient and control populations and thereby constitutes the prerequisite for meaningful phenotype- genotype correlations.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>22</s2></fA05><fA06><s2>12</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Rapid and reliable detection of exon rearrangements in various movement disorders genes by multiplex ligation-dependent probe amplification</s1></fA08><fA11 i1="01" i2="1"><s1>DJARMATI (Ana)</s1></fA11><fA11 i1="02" i2="1"><s1>GUZVIC (Miodrag)</s1></fA11><fA11 i1="03" i2="1"><s1>GRÜNEWALD (Anne)</s1></fA11><fA11 i1="04" i2="1"><s1>LANG (Anthony E.)</s1></fA11><fA11 i1="05" i2="1"><s1>PRAMSTALLER (Peter P.)</s1></fA11><fA11 i1="06" i2="1"><s1>SIMON (David K.)</s1></fA11><fA11 i1="07" i2="1"><s1>KAINDL (Angela M.)</s1></fA11><fA11 i1="08" i2="1"><s1>VIEREGGE (Peter)</s1></fA11><fA11 i1="09" i2="1"><s1>NYGREN (Anders O. H.)</s1></fA11><fA11 i1="10" i2="1"><s1>BEETZ (Christian)</s1></fA11><fA11 i1="11" i2="1"><s1>HEDRICH (Katja)</s1></fA11><fA11 i1="12" i2="1"><s1>KLEIN (Christine)</s1></fA11><fA14 i1="01"><s1>Department of Neurology, University of Lübeck</s1><s2>Liibeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Human Genetics, University of Liibeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>11 aut.</sZ></fA14><fA14 i1="03"><s1>Laboratory for Radiobiology and Molecular Genetics, Institute of Nuclear Sciences "Vinca"</s1><s2>Belgrade</s2><s3>SCG</s3><sZ>2 aut.</sZ></fA14><fA14 i1="04"><s1>Movement Disorders Centre, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>4 aut.</sZ></fA14><fA14 i1="05"><s1>Institute of Genetic Medicine, EURAC-Research</s1><s2>Bolzano-Bozen</s2><s3>ITA</s3><sZ>5 aut.</sZ></fA14><fA14 i1="06"><s1>Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>6 aut.</sZ></fA14><fA14 i1="07"><s1>Department of Pediatric Neurology, Charite University Medicine Berlin</s1><s2>Berlin</s2><s3>DEU</s3><sZ>7 aut.</sZ></fA14><fA14 i1="08"><s1>Department of Pediatric Neurology, University Hospital Dresden</s1><s2>Dresden</s2><s3>DEU</s3><sZ>7 aut.</sZ></fA14><fA14 i1="09"><s1>Department of Neurology, Hospital Lippe-Lemgo</s1><s2>Lemgo</s2><s3>DEU</s3><sZ>8 aut.</sZ></fA14><fA14 i1="10"><s1>MRC-Holland</s1><s2>Amsterdam</s2><s3>NLD</s3><sZ>9 aut.</sZ></fA14><fA14 i1="11"><s1>Institut of Clinical Chemistry and Laboratory Diagnostics, University Hospital of the Friedrich Schiller University</s1><s2>Jena</s2><s3>DEU</s3><sZ>10 aut.</sZ></fA14><fA20><s1>1708-1714</s1></fA20><fA21><s1>2007</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000143464810030</s5></fA43><fA44><s0>0000</s0><s1>© 2007 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>20 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>07-0491116</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Because of the occurrence of different types of mutations, comprehensive genetic testing for Parkinson's disease (PD), dopa-responsive dystonia (DRD), and myoclonus-dystonia (M-D) should include screening for small sequence changes and for large exonic rearrangements in disease-associated genes. In diagnostic and research settings, the latter is frequently omitted or performed by laborious and expensive quantitative real-time PCR (qPCR). Our study aimed to evaluate the utility of a novel method, multiplex ligation-dependent probe amplification (MLPA), in molecular diagnostics of movement disorders. We have analyzed, by MLPA, genomic DNA from 21 patients affected with PD, DRD, or M-D, in which the presence of exon rearrangement(s) (n = 20) or of a specific point mutation (detectable by MLPA, n = 1) had been established previously by qPCR or sequencing. In parallel, we have studied, in a blinded fashion, DNA from 49 patients with an unknown mutational status. Exon rearrangements were evident in 20 samples with previously established mutations; in the 21st sample the known specific point mutation was detected. We conclude that MLPA represents a reliable method for large-scale and cost-effective gene dosage screening of various movement disorders genes. This finding reaches far beyond a simple technical advancement and has two major implications: (1) By improving the availability of comprehensive genetic testing, it supports clinicians in the establishment of a genetically defined diagnosis; (2) By enabling gene dosage testing of several genes simultaneously, it significantly facilitates the mutational analysis of large patient and control populations and thereby constitutes the prerequisite for meaningful phenotype- genotype correlations.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC02 i1="03" i2="X"><s0>002B17A01</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Système nerveux pathologie</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Parkinson maladie</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Parkinson 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i2="X" l="FRE"><s0>Trouble neurologique</s0><s5>43</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Neurological disorder</s0><s5>43</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Trastorno neurológico</s0><s5>43</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Muscle strié pathologie</s0><s5>44</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Striated muscle disease</s0><s5>44</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Músculo estriado patología</s0><s5>44</s5></fC07><fN21><s1>323</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><affiliations><list><country><li>Allemagne</li><li>Canada</li><li>Italie</li><li>Pays-Bas</li><li>Serbie</li><li>États-Unis</li></country><region><li>Berlin</li><li>District de Dresde</li><li>Hollande-Septentrionale</li><li>Massachusetts</li><li>Saxe (Land)</li></region><settlement><li>Amsterdam</li><li>Berlin</li><li>Dresde</li></settlement></list><tree><country name="Allemagne"><noRegion><name sortKey="Djarmati, Ana" sort="Djarmati, Ana" uniqKey="Djarmati A" first="Ana" last="Djarmati">Ana Djarmati</name></noRegion><name sortKey="Beetz, Christian" sort="Beetz, Christian" uniqKey="Beetz C" first="Christian" last="Beetz">Christian Beetz</name><name sortKey="Djarmati, Ana" sort="Djarmati, Ana" uniqKey="Djarmati A" first="Ana" last="Djarmati">Ana Djarmati</name><name sortKey="Grunewald, Anne" sort="Grunewald, Anne" uniqKey="Grunewald A" first="Anne" last="Grünewald">Anne Grünewald</name><name sortKey="Grunewald, Anne" sort="Grunewald, Anne" uniqKey="Grunewald A" first="Anne" last="Grünewald">Anne Grünewald</name><name sortKey="Guzvic, Miodrag" sort="Guzvic, Miodrag" uniqKey="Guzvic M" first="Miodrag" last="Guzvic">Miodrag Guzvic</name><name sortKey="Guzvic, Miodrag" sort="Guzvic, Miodrag" uniqKey="Guzvic M" first="Miodrag" last="Guzvic">Miodrag Guzvic</name><name sortKey="Hedrich, Katja" sort="Hedrich, Katja" uniqKey="Hedrich K" first="Katja" last="Hedrich">Katja Hedrich</name><name sortKey="Hedrich, Katja" sort="Hedrich, Katja" uniqKey="Hedrich K" first="Katja" last="Hedrich">Katja Hedrich</name><name sortKey="Kaindl, Angela M" sort="Kaindl, Angela M" uniqKey="Kaindl A" first="Angela M." last="Kaindl">Angela M. Kaindl</name><name sortKey="Kaindl, Angela M" sort="Kaindl, Angela M" uniqKey="Kaindl A" first="Angela M." last="Kaindl">Angela M. Kaindl</name><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><name sortKey="Vieregge, Peter" sort="Vieregge, Peter" uniqKey="Vieregge P" first="Peter" last="Vieregge">Peter Vieregge</name><name sortKey="Vieregge, Peter" sort="Vieregge, Peter" uniqKey="Vieregge P" first="Peter" last="Vieregge">Peter Vieregge</name></country><country name="Serbie"><noRegion><name sortKey="Guzvic, Miodrag" sort="Guzvic, Miodrag" uniqKey="Guzvic M" first="Miodrag" last="Guzvic">Miodrag Guzvic</name></noRegion></country><country name="Canada"><noRegion><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name></noRegion></country><country name="Italie"><noRegion><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P." last="Pramstaller">Peter P. Pramstaller</name></noRegion></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Simon, David K" sort="Simon, David K" uniqKey="Simon D" first="David K." last="Simon">David K. Simon</name></region></country><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Nygren, Anders O H" sort="Nygren, Anders O H" uniqKey="Nygren A" first="Anders O. H." last="Nygren">Anders O. H. Nygren</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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