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https://ahro.austin.org.au/austinjspui/handle/1/22017| Title: | Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3. | Austin Authors: | Florian, Rahel T;Kraft, Florian;Leitão, Elsa;Kaya, Sabine;Klebe, Stephan;Magnin, Eloi;van Rootselaar, Anne-Fleur;Buratti, Julien;Kühnel, Theresa;Schröder, Christopher;Giesselmann, Sebastian;Tschernoster, Nikolai;Altmueller, Janine;Lamiral, Anaide;Keren, Boris;Nava, Caroline;Bouteiller, Delphine;Forlani, Sylvie;Jornea, Ludmila;Kubica, Regina;Ye, Tao;Plassard, Damien;Jost, Bernard;Meyer, Vincent;Deleuze, Jean-François;Delpu, Yannick;Avarello, Mario D M;Vijfhuizen, Lisanne S;Rudolf, Gabrielle;Hirsch, Edouard;Kroes, Thessa;Reif, Philipp S;Rosenow, Felix;Ganos, Christos;Vidailhet, Marie;Thivard, Lionel;Mathieu, Alexandre;Bourgeron, Thomas;Kurth, Ingo;Rafehi, Haloom;Steenpass, Laura;Horsthemke, Bernhard;LeGuern, Eric;Klein, Karl Martin;Labauge, Pierre;Bennett, Mark F;Bahlo, Melanie;Gecz, Jozef;Corbett, Mark A;Tijssen, Marina A J;van den Maagdenberg, Arn M J M;Depienne, Christel | Affiliation: | Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany Department of Neurology, Epilepsy Center Hessen, Philipps University, 35037, Marburg, Germany Department of Neurology-centre de référence des epilepsies rares, University Hospital of Strasbourg, 1 Avenue Molière, 67200, Strasbourg, France Institute of Human Genetics, Medical Faculty, RWTH Aachen University, 52062, Aachen, Germany AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France School of Biological Sciences, School of Medicine and Robinson Research Institute, The University of Adelaide, Adelaide, 5005, SA, Australia South Australian Health and Medical Research Institute, The University of Adelaide, Adelaide, 5005, SA, Australia Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Victoria, Australia Department of Medical Biology, University of Melbourne, Melbourne, 3010, Victoria, Australia Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands Department of Neurology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe University and LOEWE Center for Personalized Translational Epilepsy Research (CePTER), 60323, Frankfurt am Main, Germany Department of Neurology, Epilepsy Center Hessen, Philipps University, 35037, Marburg, Germany Departments of Clinical Neurosciences, Medical Genetics and Community Health Sciences, Hotchkiss Brain Institute & Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, 2500 University Dr NW, Calgary, AB, T2N 1N4, Canada APHP, Hôpital Pitié-Salpêtrière, Département de Neurologie, 75013, Paris, France IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany Department of Neurology, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany Department of Neurology, CHU Jean Minjoz, 25000, Besançon, France Departments of Neurology and Clinical Neurophysiology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany Institute of Human Genetics, Medical Faculty, RWTH Aachen University, 52062, Aachen, Germany Cologne Center for Genomics, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Weyertal 115b, 50931, Cologne, Germany Department of Neurology, CHU Jean Minjoz, 25000, Besançon, France AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France Genomic Vision, 80 Rue des Meuniers, 92220, Bagneux, France Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands Department of Neurology-centre de référence des epilepsies rares, University Hospital of Strasbourg, 1 Avenue Molière, 67200, Strasbourg, France Department of Neurology, Charité University Medicine Berlin, 10117, Berlin, Germany APHP, Hôpital Pitié-Salpêtrière, Département de Neurologie, 75013, Paris, France Human Genetics and Cognitive Functions, Pasteur Institute, UMR3571 CNRS, Université de Paris, 75015, Paris, France Institute of Human Genetics, Medical Faculty, RWTH Aachen University, 52062, Aachen, Germany Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany Department of Neurology, Gui de Chauliac University Hospital, 34295, Montpellier, France Department of Neurology, University Medical Center Groningen, University of Groningen, 9700, AB, Groningen, the Netherlands |
Issue Date: | 29-Oct-2019 | Date: | 2019 | Publication information: | Nature Communications 2019; 10(1): 4919 | Abstract: | 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/22017 | DOI: | 10.1038/s41467-019-12763-9 | ORCID: | 0000-0002-5324-9155 0000-0001-5051-9714 0000-0002-8376-9098 0000-0002-0901-0905 0000-0001-7524-6222 0000-0002-3394-2083 0000-0001-8569-6163 0000-0002-2050-3911 0000-0002-5642-8378 0000-0002-8598-8147 0000-0002-6654-1665 0000-0001-7759-8555 0000-0002-3561-6804 0000-0001-5132-0774 0000-0002-7884-6861 0000-0001-9298-3072 0000-0001-5783-571X 0000-0002-7212-9554 |
Journal: | Nature Communications | PubMed URL: | 31664039 | Type: | Journal Article |
| Appears in Collections: | Journal articles |
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