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

Media type: E-Article
Title: 5'-UTR SNP of FGF13 causes translational defect and intellectual disability
Contributor: Pan, Xingyu; Zhao, Jingrong; Zhou, Zhiying; Chen, Jijun; Yang, Zhenxing; Wu, Yuxuan; Bai, Meizhu; Jiao, Yang; Yang, Yun; Hu, Xuye; Cheng, Tianling; Lu, Qianyun; Wang, Bin; Li, Chang-Lin; Lu, Ying-Jin; Diao, Lei; Zhong, Yan-Qing; Pan, Jing; Zhu, Jianmin; Xiao, Hua-Sheng; Qiu, Zi-Long; Li, Jinsong; Wang, Zefeng; Hui, Jingyi; [...]
imprint: eLife Sciences Publications, Ltd, 2021
Published in: eLife
Language: English
DOI: 10.7554/elife.63021
ISSN: 2050-084X
Origination:
Footnote:
Description: <jats:p>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 <jats:italic>Fgf13</jats:italic> showed delayed neuronal migration during cortical development, and weakened learning and memory. Furthermore, this SNP reduced the interaction between <jats:italic>FGF13</jats:italic> 5′-UTR and polypyrimidine-tract-binding protein 2 (PTBP2), which was required for <jats:italic>FGF13</jats:italic> translation in cortical neurons. Thus, this 5′-UTR SNP of <jats:italic>FGF13</jats:italic> interferes with the translational process of <jats:italic>FGF13</jats:italic> and causes deficits in brain development and cognitive functions.</jats:p>
Access State: Open Access

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