Details

Autor(en) / Beteiligte

• Sun, Qi-Ying
• Xu, Qian
• Tian, Yun
• Hu, Zheng-Mao
• Qin, Li-Xia
• Yang, Jin-Xia
• Huang, Wen
• Xue, Jin
• Li, Jin-Chen
• Zeng, Sheng
• Wang, Ying
• Min, Hao-Xuan
• Chen, Xiao-Yu
• Wang, Jun-Pu
• Xie, Bin
• Liang, Fan
• Zhang, Hai-Nan
• Wang, Chun-Yu
• Lei, Li-Fang
• Yan, Xin-Xiang
• Xu, Hong-Wei
• Duan, Ran-Hui
• Xia, Kun
• Liu, Jing-Yu
• Jiang, Hong
• Shen, Lu
• Guo, Ji-Feng
• Tang, Bei-Sha

Titel

Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor

Ist Teil von

• Brain (London, England : 1878), 2020-01, Vol.143 (1), p.222-233

Ort / Verlag

England

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Essential tremor is one of the most common movement disorders. Despite its high prevalence and heritability, the genetic aetiology of essential tremor remains elusive. Up to now, only a few genes/loci have been identified, but these genes have not been replicated in other essential tremor families or cohorts. Here we report a genetic study in a cohort of 197 Chinese pedigrees clinically diagnosed with essential tremor. Using a comprehensive strategy combining linkage analysis, whole-exome sequencing, long-read whole-genome sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal GGC repeat expansion in the 5' region of the NOTCH2NLC gene that co-segregated with disease in 11 essential tremor families (5.58%) from our cohort. Clinically, probands that had an abnormal GGC repeat expansion were found to have more severe tremor phenotypes, lower activities of daily living ability. Obvious genetic anticipation was also detected in these 11 essential tremor-positive families. These results indicate that abnormal GGC repeat expansion in the 5' region of NOTCH2NLC gene is associated with essential tremor, and provide strong evidence that essential tremor is a family of diseases with high clinical and genetic heterogeneities.