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DOI 10.1038/s41467-019-12763-9

Медицинская библиотека · Nature communications · 2019

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

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, FAME consortium, LeGuern Eric, Klein Karl Martin, Labauge Pierre, Bennett Mark F, Bahlo Melanie, Gecz Jozef, Corbett Mark A, Tijssen Marina A J, van den Maagdenberg Arn M J M, Depienne Christel

СтатьяПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

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.

Для цитирования: 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, FAME consortium, LeGuern Eric, Klein Karl Martin, Labauge Pierre, Bennett Mark F, Bahlo Melanie, Gecz Jozef, Corbett Mark A, Tijssen Marina A J, van den Maagdenberg Arn M J M, Depienne Christel. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3.. Nature communications. 2019. DOI: 10.1038/s41467-019-12763-9.

Предметные рубрики MeSH

AdolescentAdultAgedChromosome MappingDNA Repeat ExpansionEpilepsies, MyoclonicFemaleHumansIntronsMaleMembrane ProteinsMiddle AgedPedigreeUbiquitin-Protein LigasesYoung Adult
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