Autor: |
Corrado Romano, Magnus Nordenskjöld, Tianyun Wang, Min Long, Suneeta Madan-Khetarpal, Evan E. Eichler, Jingping Zhao, Mengzhu Ou, Wei Xie, Yu Zhang, Kirsty McWalter, Chanika Phornphutkul, Kristin G. Monaghan, Koen L.I. van Gassen, Grazia M.S. Mancini, Zhengmao Hu, Madelyn A. Gillentine, Jessica Sebastian, Ying Li, Yaowen Zhang, Jieqiong Tan, Robert J. Hopkin, Kendra Hoekzema, Jozef Gecz, Lu Shen, Meilin Chen, Zhi-Qing David Xu, Carlos E. Prada, Alexander P.A. Stegmann, Judith D. Ranells, Hailun Ni, Ting Bai, Kuokuo Li, Tengfei Zhu, Joseph T. Shieh, Robert B. Hufnagel, Darius J. Adams, Lijuan Liu, Anna Lindstrand, Daryl A. Scott, Huidan Wu, Yingting Quan, Kun Xia, Melissa Racobaldo, J Peng, Mahshid Azamian, Raphael Bernier, Rongjuan Zhao, E. Haan, Fan Xia, Pengwei Peng, Nan Pang, Malin Kvarnung, Honghui Li, Xiangbin Jia, Seema R. Lalani, Jill A. Rosenfeld, Qiumeng Zhang, Susie Ball, Lin Han, Hui Guo, Ikeoluwa A. Osei-Owusu, Giuseppe Calabrese, Ornella Galesi, Tao Xu, Xiaobing Zou, Ann Nordgren, Yaning Liu, Pengfei Liu, Cenying Liu, Jonathan Pevsner, Bert B.A. de Vries, Peter M. van Hasselt |
Přispěvatelé: |
Clinical Genetics, MUMC+: DA KG Lab Centraal Lab (9), RS: FHML non-thematic output |
Rok vydání: |
2019 |
Předmět: |
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Zdroj: |
Science advances, 5(9):eaax2166. American Association for the Advancement of Science Science Advances, 5 Science advances, 5(9). American Association for the Advancement of Science Science Advances Science advances, 5(9):2166. American Association for the Advancement of Science Science Advances, 5, 9 |
ISSN: |
2375-2548 |
Popis: |
CSDE1 disruptive mutations are associated with autism. RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neurodevelopmental 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. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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