Abstract
Familial adult myoclonic epilepsy 1 (FAME1), first recognised in Japanese families, was recently shown to be caused by a TTTCA repeat insertion in intron 4 of SAMD12 on chromosome 8. We performed whole genome sequencing on two families with FAME, one of Sri Lankan origin and the other of Indian origin, and identified a TTTCA repeat insertion in SAMD12 in both families. Haplotype analysis revealed that both families shared the same core ancestral haplotype reported in Japanese and Chinese families with FAME1. Mutation dating, based on the length of shared haplotypes, estimated the age of the ancestral haplotype to be ~670 generations, or 17,000 years old. Our data extend the geographic range of this repeat expansion to Southern Asia and potentially implicate an even broader regional distribution given the age of the variant. This finding suggests patients of Asian ancestry with suspected FAME should be screened for the SAMD12 TTTCA expansion.
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Acknowledgements
We thank the families for their participation in our research and Stephanie Leech who provided research support.
Funding
MSH was supported by a National Health and Medical Research Council (NHMRC) Project Grant (1079058) and R. D. Wright Career Development Fellowship (1063799). MAC was supported by the Cerebral Palsy Alliance Research Foundation. JG was supported by NHMRC Senior Research Fellowship (1155224) and Program Grant (1091593). IES was supported by a NHMRC Program Grant (1091593) and Senior Practitioner Fellowship (1104831) and by the Health Research Council of New Zealand. SFB was supported by a NHMRC Program Grant (1091593) and Project Grant (1129054). MB was supported by a NHMRC Senior Research Fellowship (GNT1102971). This work was supported by the Victorian Government’s Operational Infrastructure Support Program and the NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS).
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IES has served on scientific advisory boards for UCB, Eisai, GlaxoSmithKline, BioMarin, Nutricia and Xenon Pharmaceuticals; editorial boards of the Annals of Neurology, Neurology and Epileptic Disorders; may accrue future revenue on pending patent WO61/010176 (filed: 2008): Therapeutic Compound; has received speaker honoraria from GlaxoSmithKline, Athena Diagnostics, UCB, BioMarin, Eisai and Transgenomics; has received funding for travel from Athena Diagnostics, UCB, Biocodex, GlaxoSmithKline, Biomarin and Eisai. The remaining authors declare no competing interests.
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Bennett, M.F., Oliver, K.L., Regan, B.M. et al. Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families. Eur J Hum Genet 28, 973–978 (2020). https://doi.org/10.1038/s41431-020-0606-z
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DOI: https://doi.org/10.1038/s41431-020-0606-z
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