Intronic (TTTGA)n insertion in SAMD12 also causes familial cortical myoclonic tremor with epilepsy.
BACKGROUND
Intronic (TTTCA)n insertions in the SAMD12, TNRC6A, and RAPGEF2 genes have been identified as causes of familial cortical myoclonic tremor with epilepsy.


OBJECTIVE
To identify the cause of familial cortical myoclonic tremor with epilepsy pedigrees without (TTTCA)n insertions in SAMD12, TNRC6A, and RAPGEF2.


METHODS
Repeat-primed polymerase chain reaction, long-range polymerase chain reaction, and Sanger sequencing were performed to identify the existence of a novel (TTTGA)n insertion. Targeted long-read sequencing was performed to confirm the accurate structure of the (TTTGA)n insertion.


RESULTS
We identified a novel expanded intronic (TTTGA)n insertion at the same site as the previously reported (TTTCA)n insertion in SAMD12. This insertion cosegregated with familial cortical myoclonic tremor with epilepsy in 1 Chinese pedigree with no (TTTCA)n insertion. In the targeted long-read sequencing of 2 patients and 1 asymptomatic carrier in this pedigree, with 1 previously reported (TTTCA)n -insertion-carrying patient as a positive control, a respective total of 302, 159, 207, and 50 on-target subreads (predicated accuracy: ≥90%) spanning the target repeat expansion region were generated. These sequencing data revealed the accurate repeat expansion structures as (TTTTA)114-123 (TTTGA)108-116 in the pedigree and (TTTTA)38 (TTTCA)479 in (TTTCA)n -insertion-carrying patient.


CONCLUSION
The targeted long-read sequencing helped us to elucidate the accurate structures of the (TTTGA)n and (TTTCA)n insertions. Our finding offers a novel possible cause for familial cortical myoclonic tremor with epilepsy and might shed light on the identification of genetic causes of this disease in pedigrees with no detected (TTTCA)n insertion in the reported causative genes. © 2019 International Parkinson and Movement Disorder Society.
['Cen|Zhidong|Z|0000-0003-3155-5781', 'Chen|You|Y|', 'Yang|Dehao|D|', 'Zhu|Qingchen|Q|', 'Chen|Si|S|', 'Chen|Xinhui|X|', 'Wang|Bo|B|', 'Xie|Fei|F|', 'Ouyang|Zhiyuan|Z|', 'Jiang|Zhengwen|Z|', 'Fu|Aisi|A|', 'Hu|Ben|B|', 'Yin|Houmin|H|', 'Qiu|Xia|X|', 'Yu|Feng|F|', 'Du|Xiaoping|X|', 'Hao|Weicheng|W|', 'Liu|Yuxi|Y|', 'Wang|Haotian|H|', 'Wang|Lebo|L|', 'Yu|Xiafei|X|', 'Xiao|Yichuan|Y|', 'Liu|Chunyu|C|', 'Xiao|Jianfeng|J|', 'Zhou|Yongxing|Y|', 'Yang|Wei|W|', 'Zhang|Baorong|B|', 'Luo|Wei|W|0000-0001-6951-7698']
D000328:Adult D044466:Asians D004831:Epilepsies, Myoclonic D006801:Humans D007438:Introns D008297:Male D009419:Nerve Tissue Proteins D010375:Pedigree D014202:Tremor
(TTTGA)n insertion SAMD12 familial cortical myoclonic tremor with epilepsy long-read sequencing