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Intronic (TTTGA) n insertion in SAMD12 also causes familial cortical myoclonic tremor with epilepsy
Author(s) -
Cen Zhidong,
Chen You,
Yang Dehao,
Zhu Qingchen,
Chen Si,
Chen Xinhui,
Wang Bo,
Xie Fei,
Ouyang Zhiyuan,
Jiang Zhengwen,
Fu Aisi,
Hu Ben,
Yin Houmin,
Qiu Xia,
Yu Feng,
Du Xiaoping,
Hao Weicheng,
Liu Yuxi,
Wang Haotian,
Wang Lebo,
Yu Xiafei,
Xiao Yichuan,
Liu Chunyu,
Xiao Jianfeng,
Zhou Yongxing,
Yang Wei,
Zhang Baorong,
Luo Wei
Publication year - 2019
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.27832
Subject(s) - sanger sequencing , epilepsy , genetics , epilepsy syndromes , insertion sequence , insertion , progressive myoclonus epilepsy , myoclonic epilepsy , biology , medicine , dna sequencing , mutation , gene , neuroscience , transposable element , genome
Abstract 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