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

Research output: Contribution to journalArticle

Abstract

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 genedisrupting 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. HITSCLIP revealed that Csde1binding targets are enriched in autismassociated 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 autismrelated syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.

Original languageEnglish (US)
Article numbereaax2166
JournalScience Advances
Volume5
Issue number9
DOIs
StatePublished - Sep 25 2019

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synapses
disabilities
seizures
proteins
Drosophila
phenotype
spine
abnormalities
neurons
genes
mice
coding
disorders
defects

All Science Journal Classification (ASJC) codes

  • Physics and Astronomy (miscellaneous)
  • General

Cite this

Guo, Hui ; Li, Ying ; Shen, Lu ; Wang, Tianyun ; Jia, Xiangbin ; Liu, Lijuan ; Xu, Tao ; Ou, Mengzhu ; Hoekzema, Kendra ; Wu, Huidan ; Gillentine, Madelyn A. ; Liu, Cenying ; Ni, Hailun ; Peng, Pengwei ; Zhao, Rongjuan ; Zhang, Yu ; Phornphutkul, Chanika ; Stegmann, Alexander P.A. ; Prada, Carlos E. ; Hopkin, Robert J. ; Shieh, Joseph T. ; McWalter, Kirsty ; Monaghan, Kristin G. ; van Hasselt, Peter M. ; van Gassen, Koen ; Bai, Ting ; Long, Min ; Han, Lin ; Quan, Yingting ; Chen, Meilin ; Zhang, Yaowen ; Li, Kuokuo ; Zhang, Qiumeng ; Tan, Jieqiong ; Zhu, Tengfei ; Liu, Yaning ; Pang, Nan ; Peng, Jing ; Scott, Daryl A. ; Lalani, Seema R. ; Azamian, Mahshid ; Mancini, Grazia M.S. ; Adams, Darius J. ; Kvarnung, Malin ; Lindstrand, Anna ; Nordgren, Ann ; Pevsner, Jonathan ; Osei-Owusu, Ikeoluwa A. ; Romano, Corrado ; Calabrese, Giuseppe ; Galesi, Ornella ; Gecz, Jozef ; Haan, Eric ; Ranells, Judith ; Racobaldo, Melissa ; Nordenskjold, Magnus ; Madan-Khetarpal, Suneeta ; Sebastian, Jessica ; Ball, Susie ; Zou, Xiaobing ; Zhao, Jingping ; Hu, Zhengmao ; Xia, Fan ; Liu, Pengfei ; Rosenfeld, Jill A. ; de Vries, Bert B.A. ; Bernier, Raphael A. ; Xu, Zhi Qing David ; Li, Honghui ; Xie, Wei ; Hufnagel, Robert B. ; Eichler, Evan E. ; Xia, Kun. / Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission. In: Science Advances. 2019 ; Vol. 5, No. 9.
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title = "Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission",
abstract = "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 genedisrupting 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. HITSCLIP revealed that Csde1binding targets are enriched in autismassociated 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 autismrelated syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.",
author = "Hui Guo and Ying Li and Lu Shen and Tianyun Wang and Xiangbin Jia and Lijuan Liu and Tao Xu and Mengzhu Ou and Kendra Hoekzema and Huidan Wu and Gillentine, {Madelyn A.} and Cenying Liu and Hailun Ni and Pengwei Peng and Rongjuan Zhao and Yu Zhang and Chanika Phornphutkul and Stegmann, {Alexander P.A.} and Prada, {Carlos E.} and Hopkin, {Robert J.} and Shieh, {Joseph T.} and Kirsty McWalter and Monaghan, {Kristin G.} and {van Hasselt}, {Peter M.} and {van Gassen}, Koen and Ting Bai and Min Long and Lin Han and Yingting Quan and Meilin Chen and Yaowen Zhang and Kuokuo Li and Qiumeng Zhang and Jieqiong Tan and Tengfei Zhu and Yaning Liu and Nan Pang and Jing Peng and Scott, {Daryl A.} and Lalani, {Seema R.} and Mahshid Azamian and Mancini, {Grazia M.S.} and Adams, {Darius J.} and Malin Kvarnung and Anna Lindstrand and Ann Nordgren and Jonathan Pevsner and Osei-Owusu, {Ikeoluwa A.} and Corrado Romano and Giuseppe Calabrese and Ornella Galesi and Jozef Gecz and Eric Haan and Judith Ranells and Melissa Racobaldo and Magnus Nordenskjold and Suneeta Madan-Khetarpal and Jessica Sebastian and Susie Ball and Xiaobing Zou and Jingping Zhao and Zhengmao Hu and Fan Xia and Pengfei Liu and Rosenfeld, {Jill A.} and {de Vries}, {Bert B.A.} and Bernier, {Raphael A.} and Xu, {Zhi Qing David} and Honghui Li and Wei Xie and Hufnagel, {Robert B.} and Eichler, {Evan E.} and Kun Xia",
year = "2019",
month = "9",
day = "25",
doi = "10.1126/sciadv.aax2166",
language = "English (US)",
volume = "5",
journal = "Indian Journal of Pure and Applied Physics",
issn = "0019-5596",
publisher = "National Institute of Science Communication and Information Resources (NISCAIR)",
number = "9",

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Guo, H, Li, Y, Shen, L, Wang, T, Jia, X, Liu, L, Xu, T, Ou, M, Hoekzema, K, Wu, H, Gillentine, MA, Liu, C, Ni, H, Peng, P, Zhao, R, Zhang, Y, Phornphutkul, C, Stegmann, APA, Prada, CE, Hopkin, RJ, Shieh, JT, McWalter, K, Monaghan, KG, van Hasselt, PM, van Gassen, K, Bai, T, Long, M, Han, L, Quan, Y, Chen, M, Zhang, Y, Li, K, Zhang, Q, Tan, J, Zhu, T, Liu, Y, Pang, N, Peng, J, Scott, DA, Lalani, SR, Azamian, M, Mancini, GMS, Adams, DJ, Kvarnung, M, Lindstrand, A, Nordgren, A, Pevsner, J, Osei-Owusu, IA, Romano, C, Calabrese, G, Galesi, O, Gecz, J, Haan, E, Ranells, J, Racobaldo, M, Nordenskjold, M, Madan-Khetarpal, S, Sebastian, J, Ball, S, Zou, X, Zhao, J, Hu, Z, Xia, F, Liu, P, Rosenfeld, JA, de Vries, BBA, Bernier, RA, Xu, ZQD, Li, H, Xie, W, Hufnagel, RB, Eichler, EE & Xia, K 2019, 'Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission', Science Advances, vol. 5, no. 9, eaax2166. https://doi.org/10.1126/sciadv.aax2166

Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission. / Guo, Hui; Li, Ying; Shen, Lu; Wang, Tianyun; Jia, Xiangbin; Liu, Lijuan; Xu, Tao; Ou, Mengzhu; Hoekzema, Kendra; Wu, Huidan; Gillentine, Madelyn A.; Liu, Cenying; Ni, Hailun; Peng, Pengwei; Zhao, Rongjuan; Zhang, Yu; Phornphutkul, Chanika; Stegmann, Alexander P.A.; Prada, Carlos E.; Hopkin, Robert J.; Shieh, Joseph T.; McWalter, Kirsty; Monaghan, Kristin G.; van Hasselt, Peter M.; van Gassen, Koen; Bai, Ting; Long, Min; Han, Lin; Quan, Yingting; Chen, Meilin; Zhang, Yaowen; Li, Kuokuo; Zhang, Qiumeng; Tan, Jieqiong; Zhu, Tengfei; Liu, Yaning; Pang, Nan; Peng, Jing; Scott, Daryl A.; Lalani, Seema R.; Azamian, Mahshid; Mancini, Grazia M.S.; Adams, Darius J.; Kvarnung, Malin; Lindstrand, Anna; Nordgren, Ann; Pevsner, Jonathan; Osei-Owusu, Ikeoluwa A.; Romano, Corrado; Calabrese, Giuseppe; Galesi, Ornella; Gecz, Jozef; Haan, Eric; Ranells, Judith; Racobaldo, Melissa; Nordenskjold, Magnus; Madan-Khetarpal, Suneeta; Sebastian, Jessica; Ball, Susie; Zou, Xiaobing; Zhao, Jingping; Hu, Zhengmao; Xia, Fan; Liu, Pengfei; Rosenfeld, Jill A.; de Vries, Bert B.A.; Bernier, Raphael A.; Xu, Zhi Qing David; Li, Honghui; Xie, Wei; Hufnagel, Robert B.; Eichler, Evan E.; Xia, Kun.

In: Science Advances, Vol. 5, No. 9, eaax2166, 25.09.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission

AU - Guo, Hui

AU - Li, Ying

AU - Shen, Lu

AU - Wang, Tianyun

AU - Jia, Xiangbin

AU - Liu, Lijuan

AU - Xu, Tao

AU - Ou, Mengzhu

AU - Hoekzema, Kendra

AU - Wu, Huidan

AU - Gillentine, Madelyn A.

AU - Liu, Cenying

AU - Ni, Hailun

AU - Peng, Pengwei

AU - Zhao, Rongjuan

AU - Zhang, Yu

AU - Phornphutkul, Chanika

AU - Stegmann, Alexander P.A.

AU - Prada, Carlos E.

AU - Hopkin, Robert J.

AU - Shieh, Joseph T.

AU - McWalter, Kirsty

AU - Monaghan, Kristin G.

AU - van Hasselt, Peter M.

AU - van Gassen, Koen

AU - Bai, Ting

AU - Long, Min

AU - Han, Lin

AU - Quan, Yingting

AU - Chen, Meilin

AU - Zhang, Yaowen

AU - Li, Kuokuo

AU - Zhang, Qiumeng

AU - Tan, Jieqiong

AU - Zhu, Tengfei

AU - Liu, Yaning

AU - Pang, Nan

AU - Peng, Jing

AU - Scott, Daryl A.

AU - Lalani, Seema R.

AU - Azamian, Mahshid

AU - Mancini, Grazia M.S.

AU - Adams, Darius J.

AU - Kvarnung, Malin

AU - Lindstrand, Anna

AU - Nordgren, Ann

AU - Pevsner, Jonathan

AU - Osei-Owusu, Ikeoluwa A.

AU - Romano, Corrado

AU - Calabrese, Giuseppe

AU - Galesi, Ornella

AU - Gecz, Jozef

AU - Haan, Eric

AU - Ranells, Judith

AU - Racobaldo, Melissa

AU - Nordenskjold, Magnus

AU - Madan-Khetarpal, Suneeta

AU - Sebastian, Jessica

AU - Ball, Susie

AU - Zou, Xiaobing

AU - Zhao, Jingping

AU - Hu, Zhengmao

AU - Xia, Fan

AU - Liu, Pengfei

AU - Rosenfeld, Jill A.

AU - de Vries, Bert B.A.

AU - Bernier, Raphael A.

AU - Xu, Zhi Qing David

AU - Li, Honghui

AU - Xie, Wei

AU - Hufnagel, Robert B.

AU - Eichler, Evan E.

AU - Xia, Kun

PY - 2019/9/25

Y1 - 2019/9/25

N2 - 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 genedisrupting 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. HITSCLIP revealed that Csde1binding targets are enriched in autismassociated 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 autismrelated syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.

AB - 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 genedisrupting 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. HITSCLIP revealed that Csde1binding targets are enriched in autismassociated 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 autismrelated syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.

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U2 - 10.1126/sciadv.aax2166

DO - 10.1126/sciadv.aax2166

M3 - Article

C2 - 31579823

AN - SCOPUS:85072635293

VL - 5

JO - Indian Journal of Pure and Applied Physics

JF - Indian Journal of Pure and Applied Physics

SN - 0019-5596

IS - 9

M1 - eaax2166

ER -