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

• DOI: 10.7554/elife.63021
• Publication Date: 2021-06-29T12:00:14Z
• Authors: 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
• Keywords: SNP

The congenital intellectual disability (ID)-causing gene mutations remain largely unclear, although many genetic variations might relate to ID. We screened in Chinese Han children suffering from severe ID and found a single-nucleotide polymorphism (SNP) 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 patient-derived induced pluripotent stem cells, this SNP reduced translation FGF13, which stabilizes microtubules developing neurons. Mice carrying homologous point mutation 5′-UTR Fgf13 showed delayed neuronal migration during cortical development, weakened learning memory. Furthermore, interaction between FGF13 polypyrimidine-tract-binding protein 2 (PTBP2), was required for Thus, interferes with translational process causes deficits brain development cognitive functions.