Publication

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

FAME consortium, Florian, R. T., Kraft, F., Leitão, E., Kaya, S., Klebe, S., Magnin, E., van Rootselaar, A-F., Buratti, J., Kühnel, T., Schröder, C., Giesselmann, S., Tschernoster, N., Altmueller, J., Lamiral, A., Keren, B., Nava, C., Bouteiller, D., Forlani, S., Jornea, L., Kubica, R., Ye, T., Plassard, D., Jost, B., Meyer, V., Deleuze, J-F., Delpu, Y., Avarello, M. D. M., Vijfhuizen, L. S., Rudolf, G., Hirsch, E., Kroes, T., Reif, P. S., Rosenow, F., Ganos, C., Vidailhet, M., Thivard, L., Mathieu, A., Bourgeron, T., Kurth, I., Rafehi, H., Steenpass, L., Horsthemke, B., LeGuern, E., Klein, K. M., Labauge, P., Bennett, M. F., Bahlo, M., Gecz, J., Corbett, M. A. & Tijssen, M. A. J., 29-Oct-2019, In : Nature Communications. 10, 1, 14 p., 4919.

Research output: Contribution to journalArticleAcademicpeer-review

APA

FAME consortium, Florian, R. T., Kraft, F., Leitão, E., Kaya, S., Klebe, S., ... Tijssen, M. A. J. (2019). Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3. Nature Communications, 10(1), [4919]. https://doi.org/10.1038/s41467-019-12763-9

Author

FAME consortium ; 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. / Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3. In: Nature Communications. 2019 ; Vol. 10, No. 1.

Harvard

FAME consortium, Florian, RT, Kraft, F, Leitão, E, Kaya, S, Klebe, S, Magnin, E, van Rootselaar, A-F, Buratti, J, Kühnel, T, Schröder, C, Giesselmann, S, Tschernoster, N, Altmueller, J, Lamiral, A, Keren, B, Nava, C, Bouteiller, D, Forlani, S, Jornea, L, Kubica, R, Ye, T, Plassard, D, Jost, B, Meyer, V, Deleuze, J-F, Delpu, Y, Avarello, MDM, Vijfhuizen, LS, Rudolf, G, Hirsch, E, Kroes, T, Reif, PS, Rosenow, F, Ganos, C, Vidailhet, M, Thivard, L, Mathieu, A, Bourgeron, T, Kurth, I, Rafehi, H, Steenpass, L, Horsthemke, B, LeGuern, E, Klein, KM, Labauge, P, Bennett, MF, Bahlo, M, Gecz, J, Corbett, MA & Tijssen, MAJ 2019, 'Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3', Nature Communications, vol. 10, no. 1, 4919. https://doi.org/10.1038/s41467-019-12763-9

Standard

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

In: Nature Communications, Vol. 10, No. 1, 4919, 29.10.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

FAME consortium, Florian RT, Kraft F, Leitão E, Kaya S, Klebe S et al. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3. Nature Communications. 2019 Oct 29;10(1). 4919. https://doi.org/10.1038/s41467-019-12763-9


BibTeX

@article{1b3985c22da7400098f70b85b22b63e2,
title = "Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3",
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.",
keywords = "CORTICAL TREMOR, LOCUS, EXCLUSION, REPEATS, LINKAGE, GENOME, SEQ, DNA",
author = "{FAME consortium} and Florian, {Rahel T} and Florian Kraft and Elsa Leit{\~a}o and Sabine Kaya and Stephan Klebe and Eloi Magnin and {van Rootselaar}, Anne-Fleur and Julien Buratti and Theresa K{\"u}hnel and Christopher Schr{\"o}der and Sebastian Giesselmann and Nikolai Tschernoster and Janine Altmueller and Anaide Lamiral and Boris Keren and Caroline Nava and Delphine Bouteiller and Sylvie Forlani and Ludmila Jornea and Regina Kubica and Tao Ye and Damien Plassard and Bernard Jost and Vincent Meyer and Jean-Fran{\cc}ois Deleuze and Yannick Delpu and Avarello, {Mario D M} and Vijfhuizen, {Lisanne S} and Gabrielle Rudolf and Edouard Hirsch and Thessa Kroes and Reif, {Philipp S} and Felix Rosenow and Christos Ganos and Marie Vidailhet and Lionel Thivard and Alexandre Mathieu and Thomas Bourgeron and Ingo Kurth and Haloom Rafehi and Laura Steenpass and Bernhard Horsthemke and Eric LeGuern and Klein, {Karl Martin} and Pierre Labauge and Bennett, {Mark F} and Melanie Bahlo and Jozef Gecz and Corbett, {Mark A} and Tijssen, {Marina A J}",
year = "2019",
month = "10",
day = "29",
doi = "10.1038/s41467-019-12763-9",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3

AU - FAME consortium

AU - Florian, Rahel T

AU - Kraft, Florian

AU - Leitão, Elsa

AU - Kaya, Sabine

AU - Klebe, Stephan

AU - Magnin, Eloi

AU - van Rootselaar, Anne-Fleur

AU - Buratti, Julien

AU - Kühnel, Theresa

AU - Schröder, Christopher

AU - Giesselmann, Sebastian

AU - Tschernoster, Nikolai

AU - Altmueller, Janine

AU - Lamiral, Anaide

AU - Keren, Boris

AU - Nava, Caroline

AU - Bouteiller, Delphine

AU - Forlani, Sylvie

AU - Jornea, Ludmila

AU - Kubica, Regina

AU - Ye, Tao

AU - Plassard, Damien

AU - Jost, Bernard

AU - Meyer, Vincent

AU - Deleuze, Jean-François

AU - Delpu, Yannick

AU - Avarello, Mario D M

AU - Vijfhuizen, Lisanne S

AU - Rudolf, Gabrielle

AU - Hirsch, Edouard

AU - Kroes, Thessa

AU - Reif, Philipp S

AU - Rosenow, Felix

AU - Ganos, Christos

AU - Vidailhet, Marie

AU - Thivard, Lionel

AU - Mathieu, Alexandre

AU - Bourgeron, Thomas

AU - Kurth, Ingo

AU - Rafehi, Haloom

AU - Steenpass, Laura

AU - Horsthemke, Bernhard

AU - LeGuern, Eric

AU - Klein, Karl Martin

AU - Labauge, Pierre

AU - Bennett, Mark F

AU - Bahlo, Melanie

AU - Gecz, Jozef

AU - Corbett, Mark A

AU - Tijssen, Marina A J

PY - 2019/10/29

Y1 - 2019/10/29

N2 - 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.

AB - 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.

KW - CORTICAL TREMOR

KW - LOCUS

KW - EXCLUSION

KW - REPEATS

KW - LINKAGE

KW - GENOME

KW - SEQ

KW - DNA

U2 - 10.1038/s41467-019-12763-9

DO - 10.1038/s41467-019-12763-9

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 4919

ER -

ID: 108224278