Florian, Rahel T., Kraft, Florian ORCID: 0000-0002-5324-9155, Leitao, Elsa ORCID: 0000-0001-5051-9714, Kaya, Sabine, Klebe, Stephan, Magnin, Eloi ORCID: 0000-0003-3036-9266, van Rootselaar, Anne-Fleur ORCID: 0000-0002-8376-9098, Buratti, Julien ORCID: 0000-0002-0901-0905, Kuehnel, Theresa, Schroeder, Christopher, Giesselmann, Sebastian, Tschernoster, Nikolai, Altmueller, Janine, lamiral, AnaiDe, Keren, Boris, Nava, Caroline ORCID: 0000-0003-1272-0518, Bouteiller, Delphine, Forlani, Sylvie, Jornea, Ludmila, Kubica, Regina, Ye, Tao, Plassard, Damien, Jost, Bernard, Meyer, Vincent, Deleuze, Jean-Francois, Delpu, Yannick, Avarello, Mario D. M., Vijfhuizen, Lisanne S., Rudolf, Gabrielle ORCID: 0000-0002-2050-3911, Hirsch, Edouard, Kroes, Thessa ORCID: 0000-0003-1416-5407, Reif, Philipp S., Rosenow, Felix, Ganos, Christos ORCID: 0000-0001-8077-8530, Vidailhet, Marie, Thivard, Lionel, Mathieu, Alexandre, Bourgeron, Thomas, Kurth, Ingo, Rafehi, Haloom, Steenpass, Laura, Horsthemke, Bernhard, Berkovic, Samuel F., Bisulli, Francesca, Brancati, Francesco, Canafoglia, Laura, Casari, Giorgio, Guerrini, Renzo, Ishiura, Hiroyuki, Licchetta, Laura, Mei, Davide, Pippucci, Tommaso, Sadleir, Lynette, Scheffer, Ingrid E., Striano, Pasquale ORCID: 0000-0002-6065-1476, Tinuper, Paolo, Tsuji, Shoji, Zara, Federico, LeGuern, Eric, Klein, Karl Martin ORCID: 0000-0002-6654-1665, Labauge, Pierre, Bennett, Mark F., Bahlo, Melanie ORCID: 0000-0001-5132-0774, Gecz, Jozef ORCID: 0000-0002-7884-6861, Corbett, Mark A., Tijssen, Marina A. J., van den Maagdenberg, Arn M. J. M. and Depienne, Christel (2019). Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Florian, Rahel T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kraft, FlorianUNSPECIFIEDorcid.org/0000-0002-5324-9155UNSPECIFIED
Leitao, ElsaUNSPECIFIEDorcid.org/0000-0001-5051-9714UNSPECIFIED
Kaya, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klebe, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Magnin, EloiUNSPECIFIEDorcid.org/0000-0003-3036-9266UNSPECIFIED
van Rootselaar, Anne-FleurUNSPECIFIEDorcid.org/0000-0002-8376-9098UNSPECIFIED
Buratti, JulienUNSPECIFIEDorcid.org/0000-0002-0901-0905UNSPECIFIED
Kuehnel, TheresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeder, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giesselmann, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tschernoster, NikolaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
lamiral, AnaiDeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keren, BorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nava, CarolineUNSPECIFIEDorcid.org/0000-0003-1272-0518UNSPECIFIED
Bouteiller, DelphineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Forlani, SylvieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jornea, LudmilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kubica, ReginaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ye, TaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plassard, DamienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jost, BernardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyer, VincentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deleuze, Jean-FrancoisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delpu, YannickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Avarello, Mario D. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vijfhuizen, Lisanne S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rudolf, GabrielleUNSPECIFIEDorcid.org/0000-0002-2050-3911UNSPECIFIED
Hirsch, EdouardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroes, ThessaUNSPECIFIEDorcid.org/0000-0003-1416-5407UNSPECIFIED
Reif, Philipp S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenow, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ganos, ChristosUNSPECIFIEDorcid.org/0000-0001-8077-8530UNSPECIFIED
Vidailhet, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thivard, LionelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mathieu, AlexandreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bourgeron, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurth, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rafehi, HaloomUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steenpass, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horsthemke, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berkovic, Samuel F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bisulli, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brancati, FrancescoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Canafoglia, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Casari, GiorgioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guerrini, RenzoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ishiura, HiroyukiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Licchetta, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mei, DavideUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pippucci, TommasoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sadleir, LynetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheffer, Ingrid E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Striano, PasqualeUNSPECIFIEDorcid.org/0000-0002-6065-1476UNSPECIFIED
Tinuper, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tsuji, ShojiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zara, FedericoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
LeGuern, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, Karl MartinUNSPECIFIEDorcid.org/0000-0002-6654-1665UNSPECIFIED
Labauge, PierreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bennett, Mark F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bahlo, MelanieUNSPECIFIEDorcid.org/0000-0001-5132-0774UNSPECIFIED
Gecz, JozefUNSPECIFIEDorcid.org/0000-0002-7884-6861UNSPECIFIED
Corbett, Mark A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tijssen, Marina A. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van den Maagdenberg, Arn M. J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Depienne, ChristelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-130243
DOI: 10.1038/s41467-019-12763-9
Journal or Publication Title: Nat. Commun.
Volume: 10
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CORTICAL TREMOR; LOCUS; EXCLUSION; REPEATS; LINKAGE; GENOME; SEQ; DNAMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13024

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