Journal article

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 Show all



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..

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Awarded by European Fund for Regional Development from the European Union

Awarded by Italian Ministry of Health

Awarded by Istituto Superiore di Sanita, Italy

Funding Acknowledgements

We wish to thank the many families involved in this study. We thank Dr. Tessa Mattiske, Dr. Mark Holloway and (Andy) Hung Nguyen for technical assistance. Dr. Joel Geoghegan and Dr. Andreas Schreiber for assistance with PacBio sequencing. We wish to acknowledge the following sources of funding: NHMRC (Jozef Gecz, Ingrid Scheffer Sam Berkovic), Women's and Children's Hospital Research Foundation (Mark Corbett, Jozef Gecz), Muir Maxwell Trust and Epilepsy Society (Simona Balestrini, Sanjay M. Sisodiya), The European Fund for Regional Development from the European Union (grant 01492947) and the province of Friesland, Dystonia Medical Research Foundation, Stichting Wetenschapsfonds Dystonie Vereniging, Fonds Psychische Gezondheid, Phelps Stichting, from Ipsen & Allergan Farmaceutics, Merz, and Actelion (Marina A.J. Tijssen). The Italian Ministry of Health (grant GR2013-02356227) and Istituto Superiore di Sanita, Italy, (grant PGR00229-PGR00919 and Farmindustria) Undiagnosed Disease Network Italy, (Francesco Brancati). The Fondation maladies rares, University Hospital Essen (Christel Depienne). This work was partly done at NIHR University College London Hospitals Biomedical Research Centre, which receives a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centres funding scheme.