5'-UTR SNP of FGF13 causes translational defect and intellectual disability.

eLife (2021-06-30)
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, Xu Zhang

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.

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Monoclonal ANTI-FLAG® M2 antibody produced in mouse, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Anti-HA antibody, Mouse monoclonal antibody produced in mouse, clone HA-7, purified from hybridoma cell culture