Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/122683
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Type: Journal article
Title: Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3
Author: 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.
et al.
Citation: Nature Communications, 2019; 10(1):4919-1-4919-14
Publisher: Springer Nature
Issue Date: 2019
ISSN: 2041-1723
2041-1723
Statement of
Responsibility: 
Rahel T. Florian … Thessa Kroes … Jozef Gecz, Mark A. Corbett … FAME Consortium … et al.
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: FAME consortium
Rights: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 1000003470
DOI: 10.1038/s41467-019-12763-9
Grant ID: http://purl.org/au-research/grants/nhmrc/GNT1054618
http://purl.org/au-research/grants/nhmrc/GNT1102971
Appears in Collections:Medicine publications

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