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; Lacomino, 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
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
Supplementary Data 1;
Supplementary Data 2;