Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia

DYT1 dystonia is an autosomal-dominantly inherited movement disorder, which is usually caused by a GAG deletion in the TOR1A gene. Due to the reduced penetrance of ∼30–40%, the determination of the mutation in a subject is of limited use with regard to actual manifestation of symptoms.In the present...

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Main Authors:	M. Walter, M. Bonin, R. Saunders Pullman, E.M. Valente, M. Loi, M. Gambarin, D. Raymond, M. Tinazzi, C. Kamm, N. Glöckle, S. Poths, T. Gasser, S.B. Bressman, C. Klein, L.J. Ozelius, O. Riess, K. Grundmann
Format:	Article
Language:	English
Published:	Elsevier 2010-05-01
Series:	Neurobiology of Disease
Subjects:	DYT1 dystonia Gene expression profiling TorsinA Penetrance
Online Access:	http://www.sciencedirect.com/science/article/pii/S096999610900374X

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collection	DOAJ
language	English
format	Article
sources	DOAJ
author	M. Walter M. Bonin R. Saunders Pullman E.M. Valente M. Loi M. Gambarin D. Raymond M. Tinazzi C. Kamm N. Glöckle S. Poths T. Gasser S.B. Bressman C. Klein L.J. Ozelius O. Riess K. Grundmann
spellingShingle	M. Walter M. Bonin R. Saunders Pullman E.M. Valente M. Loi M. Gambarin D. Raymond M. Tinazzi C. Kamm N. Glöckle S. Poths T. Gasser S.B. Bressman C. Klein L.J. Ozelius O. Riess K. Grundmann Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia Neurobiology of Disease DYT1 dystonia Gene expression profiling TorsinA Penetrance
author_facet	M. Walter M. Bonin R. Saunders Pullman E.M. Valente M. Loi M. Gambarin D. Raymond M. Tinazzi C. Kamm N. Glöckle S. Poths T. Gasser S.B. Bressman C. Klein L.J. Ozelius O. Riess K. Grundmann
author_sort	M. Walter
title	Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia
title_short	Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia
title_full	Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia
title_fullStr	Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia
title_full_unstemmed	Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia
title_sort	expression profiling in peripheral blood reveals signature for penetrance in dyt1 dystonia
publisher	Elsevier
series	Neurobiology of Disease
issn	1095-953X
publishDate	2010-05-01
description	DYT1 dystonia is an autosomal-dominantly inherited movement disorder, which is usually caused by a GAG deletion in the TOR1A gene. Due to the reduced penetrance of ∼30–40%, the determination of the mutation in a subject is of limited use with regard to actual manifestation of symptoms.In the present study, we used Affymetrix oligonucleotide microarrays to analyze global gene expression in blood samples of 15 manifesting and 15 non-manifesting mutation carriers in order to identify a susceptibility profile beyond the GAG deletion which is associated with the manifestation of symptoms in DYT1 dystonia.We identified a genetic signature which distinguished between asymptomatic mutation carriers and symptomatic DYT1 patients with 86.7% sensitivity and 100% specificity. This genetic signature could correctly predict the disease state in an independent test set with a sensitivity of 87.5% and a specificity of 85.7%.Conclusively, this genetic signature might provide a possibility to distinguish DYT1 patients from asymptomatic mutation carriers.
topic	DYT1 dystonia Gene expression profiling TorsinA Penetrance
url	http://www.sciencedirect.com/science/article/pii/S096999610900374X
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spelling	doaj-77450b67410240129d7949927c62bcbb2021-03-20T04:58:52ZengElsevierNeurobiology of Disease1095-953X2010-05-01382192200Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystoniaM. Walter0M. Bonin1R. Saunders Pullman2E.M. Valente3M. Loi4M. Gambarin5D. Raymond6M. Tinazzi7C. Kamm8N. Glöckle9S. Poths10T. Gasser11S.B. Bressman12C. Klein13L.J. Ozelius14O. Riess15K. Grundmann16Department of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Calwer Str. 7, D-72076 Tuebingen, Germany; Microarray Facility Tuebingen, Institute of Human Genetics, University of Tuebingen, Calwer Str.7, 72076 Tuebingen GermanyDepartment of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Calwer Str. 7, D-72076 Tuebingen, Germany; Microarray Facility Tuebingen, Institute of Human Genetics, University of Tuebingen, Calwer Str.7, 72076 Tuebingen GermanyDepartment of Neurology, Beth Israel Medical Center, Union Square East New York, NY 10003-3314, USA; Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USAIRCCS Casa Sollievo della Sofferenza, CSS-Mendel Institute, viale Regina Margherita 261, 00198 Rome, Italy; Department of Medical and Surgical Pediatric Sciences, University of Messina, Policlinico, Via Consolare Valeria, Pad. NI, Messina, ItalyDepartment of Neuropsychiatry, G. Brotzu Hospital, Via Peretti, Cagliari, Sardegna 09139 ItalyDepartment of Neurological and Visual Sciences, University of Verona, Policlinico “G.B. Rossi”, P.le L.A. Scuro 10, 37134 Verona, ItalyDepartment of Neurology, Beth Israel Medical Center, Union Square East New York, NY 10003-3314, USADepartment of Neurological and Visual Sciences, University of Verona, Policlinico “G.B. Rossi”, P.le L.A. Scuro 10, 37134 Verona, ItalyDepartment of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases Otfried-Müller-Straße 27, 72076 Tübingen, GermanyDepartment of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Calwer Str. 7, D-72076 Tuebingen, GermanyDepartment of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Calwer Str. 7, D-72076 Tuebingen, Germany; Microarray Facility Tuebingen, Institute of Human Genetics, University of Tuebingen, Calwer Str.7, 72076 Tuebingen GermanyDepartment of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases Otfried-Müller-Straße 27, 72076 Tübingen, GermanyDepartment of Neurology, Beth Israel Medical Center, Union Square East New York, NY 10003-3314, USASection of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Luebeck, Maria-Goeppert-Str. 1, 23562 Luebeck, GermanyDepartments of Genetics and Genomic Sciences and Neurology, Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1498, New York, NY 10029, USADepartment of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Calwer Str. 7, D-72076 Tuebingen, GermanyDepartment of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Calwer Str. 7, D-72076 Tuebingen, Germany; Corresponding author. Fax: +49 7071 5171.DYT1 dystonia is an autosomal-dominantly inherited movement disorder, which is usually caused by a GAG deletion in the TOR1A gene. Due to the reduced penetrance of ∼30–40%, the determination of the mutation in a subject is of limited use with regard to actual manifestation of symptoms.In the present study, we used Affymetrix oligonucleotide microarrays to analyze global gene expression in blood samples of 15 manifesting and 15 non-manifesting mutation carriers in order to identify a susceptibility profile beyond the GAG deletion which is associated with the manifestation of symptoms in DYT1 dystonia.We identified a genetic signature which distinguished between asymptomatic mutation carriers and symptomatic DYT1 patients with 86.7% sensitivity and 100% specificity. This genetic signature could correctly predict the disease state in an independent test set with a sensitivity of 87.5% and a specificity of 85.7%.Conclusively, this genetic signature might provide a possibility to distinguish DYT1 patients from asymptomatic mutation carriers.http://www.sciencedirect.com/science/article/pii/S096999610900374XDYT1 dystoniaGene expression profilingTorsinAPenetrance

Expression profiling in peripheral blood reveals signature for penetrance in DYT1 dystonia

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