Format

Send to

Choose Destination
Eur J Hum Genet. 2020 Mar 16. doi: 10.1038/s41431-020-0606-z. [Epub ahead of print]

Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families.

Author information

1
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
2
Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3052, Australia.
3
Epilepsy Research Centre, Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, VIC, 3084, Australia.
4
Neurology Department, Northern Health, Melbourne, VIC, 3076, Australia.
5
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, 3052, Australia.
6
Robinson Research Institute & Adelaide Medical School, The University of Adelaide, Adelaide, SA, 5005, Australia.
7
South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.
8
Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Parkville, VIC, 3052, Australia.
9
The Florey Institute, Parkville, VIC, 3052, Australia.
10
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. bahlo@wehi.edu.au.
11
Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3052, Australia. bahlo@wehi.edu.au.

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.

PMID:
32203200
DOI:
10.1038/s41431-020-0606-z

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center