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

Florian, RT; Kraft, F; Leitao, E; Kaya, S; Klebe, S; Magnin, E; van Rootselaar, AF; Buratti, J; Kuhnel, T; Schroder, 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, JF; 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; Fame consortium; LeGuern, E; Klein, KM; Labauge, P; Bennett, MF; Bahlo, M; Gecz, J; Corbett, MA; Tijssen, MAJ; van den Maagdenberg, Amjm; Depienne, C

Author(s): Florian, RT; Kraft, F; Leitao, E; Kaya, S; Klebe, S; Magnin, E; van Rootselaar, AF; Buratti, J; Kuhnel, T; Schroder, 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, JF; 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; Fame consortium; LeGuern, E; Klein, KM; Labauge, P; Bennett, MF; Bahlo, M; Gecz, J; Corbett, MA; Tijssen, MAJ; van den Maagdenberg, Amjm; Depienne, C;
Details: Publication Year 2019-10-29,Volume 10,Issue #1,Page 4919
Journal Title: Nature Communications
Publication Type: Journal Article
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.
Publisher: NPG
Research Division(s): Population Health And Immunity
PubMed ID: 31664039
Publisher's Version: https://doi.org/10.1038/s41467-019-12763-9
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-019-12763-9
NHMRC Grants: NHMRC/GNT1054618, NHMRC/GNT1102971,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2019-11-20 02:45:20

Last Modified: 2020-02-04 02:09:49