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 Rootselaar; Anthony 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

doi:10.1038/s41467-019-12671-y

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^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

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 language	English
Article number	4920
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12671-y
State	Published - 1 Dec 2019

Funding

Funders	Funder number
Ipsen & Allergan Farmaceutics, Merz, and Actelion
Muir Maxwell Trust
Simona Balestrini
UK Department of Health’s NIHR Biomedical Research Centres
Women’s and Children’s Hospital Research Foundation
Dystonia Medical Research Foundation
Stichting Wetenschapsfonds Dystonie
European Commission	01492947
National Health and Medical Research Council	628952
Epilepsy Society of Australia
Fonds Psychische Gezondheid
European Regional Development Fund
UCLH Biomedical Research Centre

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10.1038/s41467-019-12671-y

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

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title = "Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2",

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.",

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

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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

TY - JOUR

T1 - Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2

AU - Corbett, Mark A.

AU - Kroes, Thessa

AU - Veneziano, Liana

AU - Bennett, Mark F.

AU - Florian, Rahel

AU - Schneider, Amy L.

AU - Coppola, Antonietta

AU - Licchetta, Laura

AU - Franceschetti, Silvana

AU - Suppa, Antonio

AU - Wenger, Aaron

AU - Mei, Davide

AU - Pendziwiat, Manuela

AU - Kaya, Sabine

AU - Delledonne, Massimo

AU - Straussberg, Rachel

AU - Xumerle, Luciano

AU - Regan, Brigid

AU - Crompton, Douglas

AU - van Rootselaar, Anne Fleur

AU - Correll, Anthony

AU - Catford, Rachael

AU - Bisulli, Francesca

AU - Chakraborty, Shreyasee

AU - Baldassari, Sara

AU - Tinuper, Paolo

AU - Barton, Kirston

AU - Carswell, Shaun

AU - Smith, Martin

AU - Berardelli, Alfredo

AU - Carroll, Renee

AU - Gardner, Alison

AU - Friend, Kathryn L.

AU - Blatt, Ilan

AU - Iacomino, Michele

AU - Di Bonaventura, Carlo

AU - Striano, Salvatore

AU - Buratti, Julien

AU - Keren, Boris

AU - Nava, Caroline

AU - Forlani, Sylvie

AU - Rudolf, Gabrielle

AU - Hirsch, Edouard

AU - Leguern, Eric

AU - Labauge, Pierre

AU - Balestrini, Simona

AU - Sander, Josemir W.

AU - Afawi, Zaid

AU - Helbig, Ingo

AU - Ishiura, Hiroyuki

AU - Tsuji, Shoji

AU - Sisodiya, Sanjay M.

AU - Casari, Giorgio

AU - Sadleir, Lynette G.

AU - van Coller, Riaan

AU - Tijssen, Marina A.J.

AU - Klein, Karl Martin

AU - van den Maagdenberg, Arn M.J.M.

AU - Zara, Federico

AU - Guerrini, Renzo

AU - Berkovic, Samuel F.

AU - Pippucci, Tommaso

AU - Canafoglia, Laura

AU - Bahlo, Melanie

AU - Striano, Pasquale

AU - Scheffer, Ingrid E.

AU - Brancati, Francesco

AU - Depienne, Christel

AU - Gecz, Jozef

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

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

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