Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/22017
Title: Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3.
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
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, VIC, Australia
Department of Medical Biology, University of Melbourne, Melbourne, 3010, VIC, 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
EDate: 2019
Citation: 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: http://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
PubMed URL: 31664039
Type: Journal Article
Appears in Collections:Journal articles

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