De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders

Xiangbin Jia; Shujie Zhang; Senwei Tan; Bing Du; Mei He; Haisong Qin; Jia Chen; Xinyu Duan; Jingsi Luo; Fei Chen; Luping Ouyang; Jian Wang; Guodong Chen; Bin Yu; Ge Zhang; Zimin Zhang; Yongqing Lyu; Yi Huang; Jian Jiao; Jin Yun Helen Chen; Kathryn J. Swoboda; Emanuele Agolini; Antonio Novelli; Chiara Leoni; Giuseppe Zampino; Gerarda Cappuccio; Nicola Brunetti-Pierri; Benedicte Gerard; Emmanuelle Ginglinger; Julie Richer; Hugh Mcmillan; Alexandre White-Brown; Kendra Hoekzema; Raphael A. Bernier; Evangeline C. Kurtz-Nelson; Rachel K. Earl; Claartje Meddens; Marielle Alders; Meredith Fuchs; Roseline Caumes; Perrine Brunelle; Thomas Smol; Ryan Kuehl; Debra-Lynn Day-Salvatore; Kristin G. Monaghan; Michelle M. Morrow; Evan E. Eichler; Zhengmao Hu; Ling Yuan; Jieqiong Tan; Kun Xia; Yiping Shen; Hui Guo

doi:10.1126/sciadv.abo7112

De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders

Xiangbin Jia, Shujie Zhang, Senwei Tan, Bing Du, Mei He, Haisong Qin, Jia Chen, Xinyu Duan, Jingsi Luo, Fei Chen, Luping Ouyang, Jian Wang, Guodong Chen, Bin Yu, Ge Zhang, Zimin Zhang, Yongqing Lyu, Yi Huang, Jian Jiao, Jin Yun Helen ChenKathryn J. Swoboda, Emanuele Agolini, Antonio Novelli, Chiara Leoni, Giuseppe Zampino, Gerarda Cappuccio, Nicola Brunetti-Pierri, Benedicte Gerard, Emmanuelle Ginglinger, Julie Richer, Hugh Mcmillan, Alexandre White-Brown, Kendra Hoekzema, Raphael A. Bernier, Evangeline C. Kurtz-Nelson, Rachel K. Earl, Claartje Meddens, Marielle Alders, Meredith Fuchs, Roseline Caumes, Perrine Brunelle, Thomas Smol, Ryan Kuehl, Debra-Lynn Day-Salvatore, Kristin G. Monaghan, Michelle M. Morrow, Evan E. Eichler, Zhengmao Hu, Ling Yuan, Jieqiong Tan, Kun Xia, Yiping Shen, Hui Guo

Risultato della ricerca: Contributo in rivista › Articolo in rivista

Abstract

Stress granules (SGs) are cytoplasmic assemblies in response to a variety of stressors. We report a new neurodevelopmental disorder (NDD) with common features of language problems, intellectual disability, and behavioral issues caused by de novo likely gene-disruptive variants in UBAP2L, which encodes an essential regulator of SG assembly. Ubap2l haploinsufficiency in mouse led to social and cognitive impairments accompanied by disrupted neurogenesis and reduced SG formation during early brain development. On the basis of data from 40,853 individuals with NDDs, we report a nominally significant excess of de novo variants within 29 genes that are not implicated in NDDs, including 3 essential genes (G3BP1, G3BP2, and UBAP2L) in the core SG interaction network. We validated that NDD-related de novo variants in newly implicated and known NDD genes, such as CAPRIN1, disrupt the interaction of the core SG network and interfere with SG formation. Together, our findings suggest the common SG pathology in NDDs.

Lingua originale	English
pagine (da-a)	N/A-N/A
Rivista	Science advances
Volume	8
DOI	https://doi.org/10.1126/sciadv.abo7112
Stato di pubblicazione	Pubblicato - 2022

Keywords

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10.1126/sciadv.abo7112

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Jia, X., Zhang, S., Tan, S., Du, B., He, M., Qin, H., Chen, J., Duan, X., Luo, J., Chen, F., Ouyang, L., Wang, J., Chen, G., Yu, B., Zhang, G., Zhang, Z., Lyu, Y., Huang, Y., Jiao, J., ... Guo, H. (2022). De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders. Science advances, 8, N/A-N/A. https://doi.org/10.1126/sciadv.abo7112

@article{6d699832a8264f62b022fe62abc453f7,

title = "De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders",

abstract = "Stress granules (SGs) are cytoplasmic assemblies in response to a variety of stressors. We report a new neurodevelopmental disorder (NDD) with common features of language problems, intellectual disability, and behavioral issues caused by de novo likely gene-disruptive variants in UBAP2L, which encodes an essential regulator of SG assembly. Ubap2l haploinsufficiency in mouse led to social and cognitive impairments accompanied by disrupted neurogenesis and reduced SG formation during early brain development. On the basis of data from 40,853 individuals with NDDs, we report a nominally significant excess of de novo variants within 29 genes that are not implicated in NDDs, including 3 essential genes (G3BP1, G3BP2, and UBAP2L) in the core SG interaction network. We validated that NDD-related de novo variants in newly implicated and known NDD genes, such as CAPRIN1, disrupt the interaction of the core SG network and interfere with SG formation. Together, our findings suggest the common SG pathology in NDDs.",

keywords = "n/a, n/a",

author = "Xiangbin Jia and Shujie Zhang and Senwei Tan and Bing Du and Mei He and Haisong Qin and Jia Chen and Xinyu Duan and Jingsi Luo and Fei Chen and Luping Ouyang and Jian Wang and Guodong Chen and Bin Yu and Ge Zhang and Zimin Zhang and Yongqing Lyu and Yi Huang and Jian Jiao and Chen, {Jin Yun Helen} and Swoboda, {Kathryn J.} and Emanuele Agolini and Antonio Novelli and Chiara Leoni and Giuseppe Zampino and Gerarda Cappuccio and Nicola Brunetti-Pierri and Benedicte Gerard and Emmanuelle Ginglinger and Julie Richer and Hugh Mcmillan and Alexandre White-Brown and Kendra Hoekzema and Bernier, {Raphael A.} and Kurtz-Nelson, {Evangeline C.} and Earl, {Rachel K.} and Claartje Meddens and Marielle Alders and Meredith Fuchs and Roseline Caumes and Perrine Brunelle and Thomas Smol and Ryan Kuehl and Debra-Lynn Day-Salvatore and Monaghan, {Kristin G.} and Morrow, {Michelle M.} and Eichler, {Evan E.} and Zhengmao Hu and Ling Yuan and Jieqiong Tan and Kun Xia and Yiping Shen and Hui Guo",

year = "2022",

doi = "10.1126/sciadv.abo7112",

language = "English",

volume = "8",

pages = "N/A--N/A",

journal = "Science advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

}

Jia, X, Zhang, S, Tan, S, Du, B, He, M, Qin, H, Chen, J, Duan, X, Luo, J, Chen, F, Ouyang, L, Wang, J, Chen, G, Yu, B, Zhang, G, Zhang, Z, Lyu, Y, Huang, Y, Jiao, J, Chen, JYH, Swoboda, KJ, Agolini, E, Novelli, A, Leoni, C, Zampino, G, Cappuccio, G, Brunetti-Pierri, N, Gerard, B, Ginglinger, E, Richer, J, Mcmillan, H, White-Brown, A, Hoekzema, K, Bernier, RA, Kurtz-Nelson, EC, Earl, RK, Meddens, C, Alders, M, Fuchs, M, Caumes, R, Brunelle, P, Smol, T, Kuehl, R, Day-Salvatore, D-L, Monaghan, KG, Morrow, MM, Eichler, EE, Hu, Z, Yuan, L, Tan, J, Xia, K, Shen, Y & Guo, H 2022, 'De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders', Science advances, vol. 8, pagg. N/A-N/A. https://doi.org/10.1126/sciadv.abo7112

TY - JOUR

T1 - De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders

AU - Jia, Xiangbin

AU - Zhang, Shujie

AU - Tan, Senwei

AU - Du, Bing

AU - He, Mei

AU - Qin, Haisong

AU - Chen, Jia

AU - Duan, Xinyu

AU - Luo, Jingsi

AU - Chen, Fei

AU - Ouyang, Luping

AU - Wang, Jian

AU - Chen, Guodong

AU - Yu, Bin

AU - Zhang, Ge

AU - Zhang, Zimin

AU - Lyu, Yongqing

AU - Huang, Yi

AU - Jiao, Jian

AU - Chen, Jin Yun Helen

AU - Swoboda, Kathryn J.

AU - Agolini, Emanuele

AU - Novelli, Antonio

AU - Leoni, Chiara

AU - Zampino, Giuseppe

AU - Cappuccio, Gerarda

AU - Brunetti-Pierri, Nicola

AU - Gerard, Benedicte

AU - Ginglinger, Emmanuelle

AU - Richer, Julie

AU - Mcmillan, Hugh

AU - White-Brown, Alexandre

AU - Hoekzema, Kendra

AU - Bernier, Raphael A.

AU - Kurtz-Nelson, Evangeline C.

AU - Earl, Rachel K.

AU - Meddens, Claartje

AU - Alders, Marielle

AU - Fuchs, Meredith

AU - Caumes, Roseline

AU - Brunelle, Perrine

AU - Smol, Thomas

AU - Kuehl, Ryan

AU - Day-Salvatore, Debra-Lynn

AU - Monaghan, Kristin G.

AU - Morrow, Michelle M.

AU - Eichler, Evan E.

AU - Hu, Zhengmao

AU - Yuan, Ling

AU - Tan, Jieqiong

AU - Xia, Kun

AU - Shen, Yiping

AU - Guo, Hui

PY - 2022

Y1 - 2022

N2 - Stress granules (SGs) are cytoplasmic assemblies in response to a variety of stressors. We report a new neurodevelopmental disorder (NDD) with common features of language problems, intellectual disability, and behavioral issues caused by de novo likely gene-disruptive variants in UBAP2L, which encodes an essential regulator of SG assembly. Ubap2l haploinsufficiency in mouse led to social and cognitive impairments accompanied by disrupted neurogenesis and reduced SG formation during early brain development. On the basis of data from 40,853 individuals with NDDs, we report a nominally significant excess of de novo variants within 29 genes that are not implicated in NDDs, including 3 essential genes (G3BP1, G3BP2, and UBAP2L) in the core SG interaction network. We validated that NDD-related de novo variants in newly implicated and known NDD genes, such as CAPRIN1, disrupt the interaction of the core SG network and interfere with SG formation. Together, our findings suggest the common SG pathology in NDDs.

AB - Stress granules (SGs) are cytoplasmic assemblies in response to a variety of stressors. We report a new neurodevelopmental disorder (NDD) with common features of language problems, intellectual disability, and behavioral issues caused by de novo likely gene-disruptive variants in UBAP2L, which encodes an essential regulator of SG assembly. Ubap2l haploinsufficiency in mouse led to social and cognitive impairments accompanied by disrupted neurogenesis and reduced SG formation during early brain development. On the basis of data from 40,853 individuals with NDDs, we report a nominally significant excess of de novo variants within 29 genes that are not implicated in NDDs, including 3 essential genes (G3BP1, G3BP2, and UBAP2L) in the core SG interaction network. We validated that NDD-related de novo variants in newly implicated and known NDD genes, such as CAPRIN1, disrupt the interaction of the core SG network and interfere with SG formation. Together, our findings suggest the common SG pathology in NDDs.

KW - n/a

UR - http://hdl.handle.net/10807/304676

U2 - 10.1126/sciadv.abo7112

DO - 10.1126/sciadv.abo7112

M3 - Article

SN - 2375-2548

VL - 8

SP - N/A-N/A

JO - Science advances

JF - Science advances

ER -

De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders

Abstract

Keywords

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