- Artikel / Aufsatz
- Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial…
Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3.
- Zugehörige Organisation
- Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
- ORCID
- 0000-0002-5324-9155
- Zugehörige Organisation
- Institute of Human Genetics, Medical Faculty, RWTH Aachen University, 52062, Aachen, Germany.
- ORCID
- 0000-0001-5051-9714
- Zugehörige Organisation
- Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
- Zugehörige Organisation
- Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
- GND
- 123761743
- Zugehörige Organisation
- Department of Neurology, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
- Zugehörige Organisation
- Department of Neurology, CHU Jean Minjoz, 25000, Besançon, France.
- ORCID
- 0000-0002-8376-9098
- Zugehörige Organisation
- Departments of Neurology and Clinical Neurophysiology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
- ORCID
- 0000-0002-0901-0905
- Zugehörige Organisation
- AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France.
- GND
- 1216509018
- Zugehörige Organisation
- Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
- Zugehörige Organisation
- Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
- Zugehörige Organisation
- Institute of Human Genetics, Medical Faculty, RWTH Aachen University, 52062, Aachen, Germany.
- Zugehörige Organisation
- Cologne Center for Genomics, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Weyertal 115b, 50931, Cologne, Germany.
- Zugehörige Organisation
- Cologne Center for Genomics, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Weyertal 115b, 50931, Cologne, Germany.
- ORCID
- 0000-0001-7524-6222
- Zugehörige Organisation
- Department of Neurology, CHU Jean Minjoz, 25000, Besançon, France.
- Zugehörige Organisation
- AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France.
- Zugehörige Organisation
- AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France.
- Zugehörige Organisation
- Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.
- Zugehörige Organisation
- Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.
- Zugehörige Organisation
- Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.
- Zugehörige Organisation
- Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
- ORCID
- 0000-0002-3394-2083
- Zugehörige Organisation
- IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France.
- ORCID
- 0000-0001-8569-6163
- Zugehörige Organisation
- IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France.
- Zugehörige Organisation
- IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France.
- Zugehörige Organisation
- Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France.
- Zugehörige Organisation
- Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France.
- Zugehörige Organisation
- Genomic Vision, 80 Rue des Meuniers, 92220, Bagneux, France.
- Zugehörige Organisation
- Genomic Vision, 80 Rue des Meuniers, 92220, Bagneux, France.
- Zugehörige Organisation
- Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands.
- ORCID
- 0000-0002-2050-3911
- Zugehörige Organisation
- IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France.
- Zugehörige Organisation
- Department of Neurology-centre de référence des epilepsies rares, University Hospital of Strasbourg, 1 Avenue Molière, 67200, Strasbourg, France.
- Zugehörige Organisation
- School of Biological Sciences, School of Medicine and Robinson Research Institute, The University of Adelaide, Adelaide, 5005, SA, Australia.
- Zugehörige Organisation
- Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe University and LOEWE Center for Personalized Translational Epilepsy Research (CePTER), 60323, Frankfurt am Main, Germany.
- Zugehörige Organisation
- Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe University and LOEWE Center for Personalized Translational Epilepsy Research (CePTER), 60323, Frankfurt am Main, Germany.
- Zugehörige Organisation
- Department of Neurology, Charité University Medicine Berlin, 10117, Berlin, Germany.
- Zugehörige Organisation
- Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.
- Zugehörige Organisation
- APHP, Hôpital Pitié-Salpêtrière, Département de Neurologie, 75013, Paris, France.
- Zugehörige Organisation
- Human Genetics and Cognitive Functions, Pasteur Institute, UMR3571 CNRS, Université de Paris, 75015, Paris, France.
- Zugehörige Organisation
- Human Genetics and Cognitive Functions, Pasteur Institute, UMR3571 CNRS, Université de Paris, 75015, Paris, France.
- ORCID
- 0000-0002-5642-8378
- Zugehörige Organisation
- Institute of Human Genetics, Medical Faculty, RWTH Aachen University, 52062, Aachen, Germany.
- Zugehörige Organisation
- Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, VIC, Australia.
- Zugehörige Organisation
- Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
- GND
- 172144035
- ORCID
- 0000-0002-8598-8147
- LSF
- 14406
- Zugehörige Organisation
- Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
- Zugehörige Organisation
- AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France.
- ORCID
- 0000-0002-6654-1665
- Zugehörige Organisation
- Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe University and LOEWE Center for Personalized Translational Epilepsy Research (CePTER), 60323, Frankfurt am Main, Germany.
- ORCID
- 0000-0001-7759-8555
- Zugehörige Organisation
- Department of Neurology, Gui de Chauliac University Hospital, 34295, Montpellier, France.
- ORCID
- 0000-0002-3561-6804
- Zugehörige Organisation
- Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, VIC, Australia.
- ORCID
- 0000-0001-5132-0774
- Zugehörige Organisation
- Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, VIC, Australia.
- ORCID
- 0000-0002-7884-6861
- Zugehörige Organisation
- School of Biological Sciences, School of Medicine and Robinson Research Institute, The University of Adelaide, Adelaide, 5005, SA, Australia.
- ORCID
- 0000-0001-9298-3072
- Zugehörige Organisation
- School of Biological Sciences, School of Medicine and Robinson Research Institute, The University of Adelaide, Adelaide, 5005, SA, Australia.
- ORCID
- 0000-0001-5783-571X
- Zugehörige Organisation
- Department of Neurology, University Medical Center Groningen, University of Groningen, 9700, AB, Groningen, the Netherlands.
- Zugehörige Organisation
- Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands.
- ORCID
- 0000-0002-7212-9554
- Zugehörige Organisation
- Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany. christel.depienne@uni-due.de.
Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements.
Vorschau
Einordnung
- Erschienen in:
-
(29.10.2019) - Datum der Veröffentlichung:
- 29.10.2019
- URN:
- urn:nbn:de:hbz:464-20191202-144513-7
- DOI:
- 10.1038/s41467-019-12763-9
- Sprache:
- Englisch
- Ressourcentyp
: - Text
- Kollektion:
- E-Publikationen
- Sachgruppen der Deutschen Nationalbibliographie:
- 610 Medizin, Gesundheit
- Einrichtung:
- Medizinische Fakultät, Universitätsklinikum Essen, Institut für Humangenetik
- Einrichtung:
- Medizinische Fakultät, Universitätsklinikum Essen, Klinik für Neurologie
- Informationen zur Erstveröffentlichung:
- Nature Communications (2019) 10:4919; Published: 29 October 2019
- Förderung:
-
The publication of this article was supported by the Publication Fund of the University of Duisburg-Essen.
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DOI (10.1038/s41467-019-12763-9)
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