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

2019-10-29

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

Journal Article

0000-0001-9298-3072

0000-0002-9921-8450

0000-0002-3561-6804

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0000-0001-9903-5550

0000-0001-6790-6251

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0000-0003-4518-3958

0000-0002-8376-9098

0000-0003-4851-2796

0000-0002-0901-0905

0000-0002-2050-3911

0000-0001-5639-1969

0000-0003-2975-7309

0000-0001-5602-5686

0000-0002-0115-8980

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0000-0001-5783-571X

0000-0002-6654-1665

0000-0002-7272-7079

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0000-0002-6065-1476

0000-0002-2311-2174

0000-0003-3624-2354

0000-0002-7212-9554

0000-0002-7884-6861

10.1038/s41467-019-12671-y

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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Nature Communications 2019; 10(1): 4920

Nature Communications