Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission

Hui Guo*, Ying Li, Lu Shen, Tianyun Wang, Xiangbin Jia, Lijuan Liu, Tao Xu, Mengzhu Ou, Kendra Hoekzema, Huidan Wu, Madelyn A. Gillentine, Cenying Liu, Hailun Ni, Pengwei Peng, Rongjuan Zhao, Yu Zhang, Chanika Phornphutkul, Alexander P. A. Stegmann, Carlos E. Prada, Robert J. HopkinJoseph T. Shieh, Kirsty McWalter, Kristin G. Monaghan, Peter M. van Hasselt, Koen van Gassen, Ting Bai, Min Long, Lin Han, Yingting Quan, Meilin Chen, Yaowen Zhang, Kuokuo Li, Qiumeng Zhang, Jieqiong Tan, Tengfei Zhu, Yaning Liu, Nan Pang, Jing Peng, Daryl A. Scott, Seema R. Lalani, Mahshid Azamian, Grazia M. S. Mancini, Darius J. Adams, Malin Kvarnung, Anna Lindstrand, Ann Nordgren, Jonathan Pevsner, Ikeoluwa A. Osei-Owusu, Corrado Romano, Giuseppe Calabrese, Ornella Galesi, Jozef Gecz, Eric Haan, Judith Ranells, Melissa Racobaldo, Magnus Nordenskjold, Suneeta Madan-Khetarpal, Jessica Sebastian, Susie Ball, Xiaobing Zou, Jingping Zhao, Zhengmao Hu, Fan Xia, Pengfei Liu, Jill A. Rosenfeld, Bert B. A. de Vries, Raphael A. Bernier, Zhi-Qing David Xu, Honghui Li, Wei Xie, Robert B. Hufnagel*, Evan E. Eichler*, Kun Xia*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Web of Science)


RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neuro-developmental and neuropsychiatric disorders. Here, we report a significant burden of heterozygous, likely gene-disrupting variants in CSDE1 (encoding a highly constrained RNA binding protein) among patients with autism and related neurodevelopmental disabilities. Analysis of 17 patients identifies common phenotypes including autism, intellectual disability, language and motor delay, seizures, macrocephaly, and variable ocular abnormalities. HITS-CLIP revealed that Csde1-binding targets are enriched in autism-associated gene sets, especially FMRP targets, and in neuronal development and synaptic plasticity-related pathways. Csde1 knockdown in primary mouse cortical neurons leads to an overgrowth of the neurites and abnormal dendritic spine morphology/synapse formation and impaired synaptic transmission, whereas mutant and knockdown experiments in Drosophila result in defects in synapse growth and synaptic transmission. Our study defines a new autism-related syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.

Original languageEnglish
Article number2166
Number of pages16
JournalScience advances
Issue number9
Publication statusPublished - Sept 2019


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