TEP1 is a risk gene for sporadic cerebral palsy
TEP1 is a risk gene for sporadic cerebral palsy
复制标题
DOI：
10.1016/j.jgg.2021.08.010
复制
发表时间：
2021
影响因子：
5.9
通讯作者：
Xing Qinghe
中科院分区：
文献类型：
--
作者：
Wang Yangong;Xu Yiran;Li Hongwei;Tang Tianxiang;Qiao Yimeng;Cheng Ye;Zhang Lingling;Song Juan;Su Yu;Zhang Xiaoli;Wang Jun;Shang Qing;Song Lili;Gao Chao;Zhu Dengna;Wang Xiaoyang;Zhu Changlian;Xing Qinghe
Cerebral palsy (CP) is a nonprogressive dyskinesia syndrome caused by early brain injury, with an incidence of approximately 2.0e3.5/1000 live births worldwide (Li et al., 2021; Moreno-De- Luca et al., 2021). Currently, there are more than 300,000 children aged 0e6 years diagnosed with CP in China (Liu et al., 1999; Yang et al., 2021), thus making it one of the most common debilitating diseases affecting children. Increasing evidence supports genetic factors as one of the causes in the pathogenesis of CP (Moreno-De- Luca et al., 2012). To date, only a few pathogenic genes have been identified (Moreno-De-Luca et al., 2012; Jin et al., 2020; Li et al., 2021; Moreno-De-Luca et al., 2021), but previous estimates suggest that hundreds of genes potentially associated with CP remain undiscovered (O'Callaghan et al., 2009; Fahey et al., 2017). In our previous work, we searched for de novo mutations in 250 parent-offspring CP trios and successfully matched 4 CP cases with de novo mutations in TEP1, identifying 1 stop-gain mutation (exon50: c.C7090T: p.R2364X), 2 frameshift deletions (exon41:c.5965delG:p.D1989fs and exon2:c.472_475del:p.R158fs), and 1 splicing mutation (exon31:c.4425-2A>C) (Jin et al., 2020). These findings suggest a potential role for telomerase-related protein 1 (TEP1) in the pathogenesis of CP. The highly conserved TEP1 gene, first described by Harrington et al. (1997), is located on chromosome 14 (14q11.2) and encodes a protein consisting of 2627 amino acids with relatively high sequence similarity to Tetrahymena telomerase protein p80. The TEP1 protein contains 1 N-terminal repeat domain, 1 RNA binding domain, 1 ATP/GTP binding motif, and 16 C-terminal WD40 repeats (also known as WD or beta-transducing repeats) (Kickhoefer et al., 2001). The available studies on TEP1 have mainly focused on its involvement in tumors and male infertility (Liu et al., 2000; Gangwani et al., 2020), and the actual biological function of TEP1 remains unclear.
