1. 5'-UTR SNP of FGF13 causes translational defect and intellectual disability
- Author
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Xu Zhang, Hua-Sheng Xiao, Tianling Cheng, Yang Jiao, Zilong Qiu, Xu-Ye Hu, Zhiying Zhou, Yuxuan Wu, Zhenxing Yang, Bin Wang, Xingyu Pan, Meizhu Bai, Jing Pan, Qianyun Lu, Jianmin Zhu, Jingyi Hui, Jinsong Li, Zefeng Wang, Lei Diao, Chang-Lin Li, Yan-Qing Zhong, Jijun Chen, Ying-Jin Lu, Jingrong Zhao, Lan Bao, and Yun Yang
- Subjects
Untranslated region ,Five prime untranslated region ,QH301-705.5 ,Science ,Intellectual disability ,Single-nucleotide polymorphism ,Biology ,Gene mutation ,polypyrimidine-tract-binding protein 2 ,General Biochemistry, Genetics and Molecular Biology ,SNP ,Biology (General) ,protein translation ,Genetics ,5'-untranslated region ,Messenger RNA ,General Immunology and Microbiology ,General Neuroscience ,Point mutation ,HEK 293 cells ,General Medicine ,single-nucleotide polymorphism ,fibroblast growth factor 13 ,Medicine - 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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