Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3 - Institut Pasteur Access content directly
Journal Articles Nature Communications Year : 2019

Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3

1 Institute of Human Genetics - Institut für Humangenetik [Essen]
2 RWTH - Rheinisch-Westfälische Technische Hochschule Aachen University
3 Uniklinik Essen - Universitätsklinikum Essen [Universität Duisburg-Essen]
4 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
5 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
6 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
7 Amsterdam Neuroscience [Pays-Bas]
8 CHU Pitié-Salpêtrière [AP-HP]
9 CMMC - Centre for Molecular Medicine Cologne [Cologne]
10 CCG - Cologne Center for Genomics [Cologne]
11 ICM - Institut du Cerveau = Paris Brain Institute
12 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
13 JACOB - Institut de Biologie François JACOB
14 CNG - Centre National de Génotypage
15 genomic vision
16 LUMC - Leiden University Medical Center
17 CRéER - Centre de référence des épilepsies rares [CHRU Strasbourg]
18 Service de Neurologie [Strasbourg]
19 School of Biological Sciences [Adelaïde]
20 University of Adelaide
21 Goethe-University Frankfurt am Main
22 Philipps Universität Marburg = Philipps University of Marburg
23 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
24 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
25 WEHI - The Walter and Eliza Hall Institute of Medical Research
26 University of Melbourne
27 Epilepsy Research Centre
28 University of Calgary
29 Hôpital Gui de Chauliac [CHU Montpellier]
30 SAHMRI - South Australian Health and Medical Research Institute [ Adelaide]
31 UMCG - University Medical Center Groningen [Groningen]
Julien Buratti
Boris Keren
Yannick Delpu
  • Function : Author
Mario Avarello
  • Function : Author
Pierre Labauge
Mark Corbett


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.
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Dates and versions

pasteur-02562487 , version 1 (04-05-2020)





Rahel Florian, Florian Kraft, Elsa Leitão, Sabine Kaya, Stephan Klebe, et al.. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3. Nature Communications, 2019, 10 (1), pp.4919. ⟨10.1038/s41467-019-12763-9⟩. ⟨pasteur-02562487⟩
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