Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2

Mark A. Corbett, Thessa Kroes, Liana Veneziano, Mark F. Bennett, Rahel Florian, Amy L. Schneider, Antonietta Coppola, Laura Licchetta, Silvana Franceschetti, Antonio Suppa, Aaron Wenger, Davide Mei, Manuela Pendziwiat, Sabine Kaya, Massimo Delledonne, Rachel Straussberg, Luciano Xumerle, Brigid Regan, Douglas Crompton, Anne Fleur van RootselaarAnthony Correll, Rachael Catford, Francesca Bisulli, Shreyasee Chakraborty, Sara Baldassari, Paolo Tinuper, Kirston Barton, Shaun Carswell, Martin Smith, Alfredo Berardelli, Renee Carroll, Alison Gardner, Kathryn L. Friend, Ilan Blatt, Michele Iacomino, Carlo Di Bonaventura, Salvatore Striano, Julien Buratti, Boris Keren, Caroline Nava, Sylvie Forlani, Gabrielle Rudolf, Edouard Hirsch, Eric Leguern, Pierre Labauge, Simona Balestrini, Josemir W. Sander, Zaid Afawi, Ingo Helbig, Hiroyuki Ishiura, Shoji Tsuji, Sanjay M. Sisodiya, Giorgio Casari, Lynette G. Sadleir, Riaan van Coller, Marina A.J. Tijssen, Karl Martin Klein, Arn M.J.M. van den Maagdenberg, Federico Zara, Renzo Guerrini, Samuel F. Berkovic, Tommaso Pippucci, Laura Canafoglia, Melanie Bahlo, Pasquale Striano, Ingrid E. Scheffer, Francesco Brancati, Christel Depienne, Jozef Gecz

Research output: Contribution to journalArticle

Abstract

Familial Adult Myoclonic Epilepsy (FAME) is characterised by cortical myoclonic tremor usually from the second decade of life and overt myoclonic or generalised tonic-clonic seizures. Four independent loci have been implicated in FAME on chromosomes (chr) 2, 3, 5 and 8. Using whole genome sequencing and repeat primed PCR, we provide evidence that chr2-linked FAME (FAME2) is caused by an expansion of an ATTTC pentamer within the first intron of STARD7. The ATTTC expansions segregate in 158/158 individuals typically affected by FAME from 22 pedigrees including 16 previously reported families recruited worldwide. RNA sequencing from patient derived fibroblasts shows no accumulation of the AUUUU or AUUUC repeat sequences and STARD7 gene expression is not affected. These data, in combination with other genes bearing similar mutations that have been implicated in FAME, suggest ATTTC expansions may cause this disorder, irrespective of the genomic locus involved.

Original languageEnglish
Article number4920
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

Fingerprint

epilepsy
Myoclonic Epilepsy
Chromosomes, Human, Pair 2
chromosomes
Chromosomes
expansion
Bearings (structural)
Genes
sequencing
loci
Fibroblasts
Gene expression
Introns
seizures
RNA Sequence Analysis
tremors
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 3
RNA
genome

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Corbett, M. A., Kroes, T., Veneziano, L., Bennett, M. F., Florian, R., Schneider, A. L., ... Gecz, J. (2019). Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2. Nature Communications, 10(1), [4920]. https://doi.org/10.1038/s41467-019-12671-y

Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2. / Corbett, Mark A.; Kroes, Thessa; Veneziano, Liana; Bennett, Mark F.; Florian, Rahel; Schneider, Amy L.; Coppola, Antonietta; Licchetta, Laura; Franceschetti, Silvana; Suppa, Antonio; Wenger, Aaron; Mei, Davide; Pendziwiat, Manuela; Kaya, Sabine; Delledonne, Massimo; Straussberg, Rachel; Xumerle, Luciano; Regan, Brigid; Crompton, Douglas; van Rootselaar, Anne Fleur; Correll, Anthony; Catford, Rachael; Bisulli, Francesca; Chakraborty, Shreyasee; Baldassari, Sara; Tinuper, Paolo; Barton, Kirston; Carswell, Shaun; Smith, Martin; Berardelli, Alfredo; Carroll, Renee; Gardner, Alison; Friend, Kathryn L.; Blatt, Ilan; Iacomino, Michele; Di Bonaventura, Carlo; Striano, Salvatore; Buratti, Julien; Keren, Boris; Nava, Caroline; Forlani, Sylvie; Rudolf, Gabrielle; Hirsch, Edouard; Leguern, Eric; Labauge, Pierre; Balestrini, Simona; Sander, Josemir W.; Afawi, Zaid; Helbig, Ingo; Ishiura, Hiroyuki; Tsuji, Shoji; Sisodiya, Sanjay M.; Casari, Giorgio; Sadleir, Lynette G.; van Coller, Riaan; Tijssen, Marina A.J.; Klein, Karl Martin; van den Maagdenberg, Arn M.J.M.; Zara, Federico; Guerrini, Renzo; Berkovic, Samuel F.; Pippucci, Tommaso; Canafoglia, Laura; Bahlo, Melanie; Striano, Pasquale; Scheffer, Ingrid E.; Brancati, Francesco; Depienne, Christel; Gecz, Jozef.

In: Nature Communications, Vol. 10, No. 1, 4920, 01.12.2019.

Research output: Contribution to journalArticle

Corbett, MA, Kroes, T, Veneziano, L, Bennett, MF, Florian, R, Schneider, AL, Coppola, A, Licchetta, L, Franceschetti, S, Suppa, A, Wenger, A, Mei, D, Pendziwiat, M, Kaya, S, Delledonne, M, Straussberg, R, Xumerle, L, Regan, B, Crompton, D, van Rootselaar, AF, Correll, A, Catford, R, Bisulli, F, Chakraborty, S, Baldassari, S, Tinuper, P, Barton, K, Carswell, S, Smith, M, Berardelli, A, Carroll, R, Gardner, A, Friend, KL, Blatt, I, Iacomino, M, Di Bonaventura, C, Striano, S, Buratti, J, Keren, B, Nava, C, Forlani, S, Rudolf, G, Hirsch, E, Leguern, E, Labauge, P, Balestrini, S, Sander, JW, Afawi, Z, Helbig, I, Ishiura, H, Tsuji, S, Sisodiya, SM, Casari, G, Sadleir, LG, van Coller, R, Tijssen, MAJ, Klein, KM, van den Maagdenberg, AMJM, Zara, F, Guerrini, R, Berkovic, SF, Pippucci, T, Canafoglia, L, Bahlo, M, Striano, P, Scheffer, IE, Brancati, F, Depienne, C & Gecz, J 2019, 'Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2', Nature Communications, vol. 10, no. 1, 4920. https://doi.org/10.1038/s41467-019-12671-y
Corbett, Mark A. ; Kroes, Thessa ; Veneziano, Liana ; Bennett, Mark F. ; Florian, Rahel ; Schneider, Amy L. ; Coppola, Antonietta ; Licchetta, Laura ; Franceschetti, Silvana ; Suppa, Antonio ; Wenger, Aaron ; Mei, Davide ; Pendziwiat, Manuela ; Kaya, Sabine ; Delledonne, Massimo ; Straussberg, Rachel ; Xumerle, Luciano ; Regan, Brigid ; Crompton, Douglas ; van Rootselaar, Anne Fleur ; Correll, Anthony ; Catford, Rachael ; Bisulli, Francesca ; Chakraborty, Shreyasee ; Baldassari, Sara ; Tinuper, Paolo ; Barton, Kirston ; Carswell, Shaun ; Smith, Martin ; Berardelli, Alfredo ; Carroll, Renee ; Gardner, Alison ; Friend, Kathryn L. ; Blatt, Ilan ; Iacomino, Michele ; Di Bonaventura, Carlo ; Striano, Salvatore ; Buratti, Julien ; Keren, Boris ; Nava, Caroline ; Forlani, Sylvie ; Rudolf, Gabrielle ; Hirsch, Edouard ; Leguern, Eric ; Labauge, Pierre ; Balestrini, Simona ; Sander, Josemir W. ; Afawi, Zaid ; Helbig, Ingo ; Ishiura, Hiroyuki ; Tsuji, Shoji ; Sisodiya, Sanjay M. ; Casari, Giorgio ; Sadleir, Lynette G. ; van Coller, Riaan ; Tijssen, Marina A.J. ; Klein, Karl Martin ; van den Maagdenberg, Arn M.J.M. ; Zara, Federico ; Guerrini, Renzo ; Berkovic, Samuel F. ; Pippucci, Tommaso ; Canafoglia, Laura ; Bahlo, Melanie ; Striano, Pasquale ; Scheffer, Ingrid E. ; Brancati, Francesco ; Depienne, Christel ; Gecz, Jozef. / Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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abstract = "Familial Adult Myoclonic Epilepsy (FAME) is characterised by cortical myoclonic tremor usually from the second decade of life and overt myoclonic or generalised tonic-clonic seizures. Four independent loci have been implicated in FAME on chromosomes (chr) 2, 3, 5 and 8. Using whole genome sequencing and repeat primed PCR, we provide evidence that chr2-linked FAME (FAME2) is caused by an expansion of an ATTTC pentamer within the first intron of STARD7. The ATTTC expansions segregate in 158/158 individuals typically affected by FAME from 22 pedigrees including 16 previously reported families recruited worldwide. RNA sequencing from patient derived fibroblasts shows no accumulation of the AUUUU or AUUUC repeat sequences and STARD7 gene expression is not affected. These data, in combination with other genes bearing similar mutations that have been implicated in FAME, suggest ATTTC expansions may cause this disorder, irrespective of the genomic locus involved.",
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