1. 5'-UTR SNP of FGF13 causes translational defect and intellectual disability
- Author
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Xingyu Pan, Jingrong Zhao, Zhiying Zhou, Jijun Chen, Zhenxing Yang, Yuxuan Wu, Meizhu Bai, Yang Jiao, Yun Yang, Xuye Hu, Tianling Cheng, Qianyun Lu, Bin Wang, Chang-Lin Li, Ying-Jin Lu, Lei Diao, Yan-Qing Zhong, Jing Pan, Jianmin Zhu, Hua-Sheng Xiao, Zi-Long Qiu, Jinsong Li, Zefeng Wang, Jingyi Hui, Lan Bao, and Xu Zhang
- Subjects
Intellectual disability ,fibroblast growth factor 13 ,single-nucleotide polymorphism ,5'-untranslated region ,protein translation ,polypyrimidine-tract-binding protein 2 ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The congenital intellectual disability (ID)-causing gene mutations remain largely unclear, although many genetic variations might relate to ID. We screened gene mutations in Chinese Han children suffering from severe ID and found a single-nucleotide polymorphism (SNP) in the 5′-untranslated region (5′-UTR) of fibroblast growth factor 13 (FGF13) mRNA (NM_001139500.1:c.-32c>G) shared by three male children. In both HEK293 cells and patient-derived induced pluripotent stem cells, this SNP reduced the translation of FGF13, which stabilizes microtubules in developing neurons. Mice carrying the homologous point mutation in 5′-UTR of Fgf13 showed delayed neuronal migration during cortical development, and weakened learning and memory. Furthermore, this SNP reduced the interaction between FGF13 5′-UTR and polypyrimidine-tract-binding protein 2 (PTBP2), which was required for FGF13 translation in cortical neurons. Thus, this 5′-UTR SNP of FGF13 interferes with the translational process of FGF13 and causes deficits in brain development and cognitive functions.
- Published
- 2021
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