Monoallelic loss-of-function variants in GSK3B lead to autism and developmental delay
De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de n...
Saved in:
Published in | Molecular psychiatry Vol. 30; no. 5; pp. 1952 - 1965 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.05.2025
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
ISSN | 1359-4184 1476-5578 1476-5578 |
DOI | 10.1038/s41380-024-02806-z |
Cover
Abstract | De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de novo potential splicing-disrupting variants (PSDVs) in 5048 probands compared to 4090 unaffected siblings. We identified 55 genes with recurrent de novo PSDVs that were highly intolerant to variation. Forty-six of these genes have not been strongly implicated in ASD or other neurodevelopmental disorders previously, including
GSK3B
. Through international, multicenter collaborations, we assembled genotype and phenotype data for 15 individuals with
GSK3B
variants and identified common phenotypes including developmental delay, ASD, sleeping disturbance, and aggressive behavior. Using available single-cell transcriptomic data, we show that
GSK3B
is enriched in dorsal progenitors and intermediate forms of excitatory neurons in the developing brain. We showed that
Gsk3b
knockdown in mouse excitatory neurons interferes with dendrite arborization and spine maturation which could not be rescued by de novo missense variants identified from affected individuals. In summary, our findings suggest that PSDVs may play an important role in the genetic etiology of ASD and allow for the prioritization of new ASD candidate genes. Importantly, we show that genetic variation resulting in
GSK3B
loss-of-function can lead to a neurodevelopmental disorder with core features of ASD and developmental delay. |
---|---|
AbstractList | De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de novo potential splicing-disrupting variants (PSDVs) in 5048 probands compared to 4090 unaffected siblings. We identified 55 genes with recurrent de novo PSDVs that were highly intolerant to variation. Forty-six of these genes have not been strongly implicated in ASD or other neurodevelopmental disorders previously, including GSK3B. Through international, multicenter collaborations, we assembled genotype and phenotype data for 15 individuals with GSK3B variants and identified common phenotypes including developmental delay, ASD, sleeping disturbance, and aggressive behavior. Using available single-cell transcriptomic data, we show that GSK3B is enriched in dorsal progenitors and intermediate forms of excitatory neurons in the developing brain. We showed that Gsk3b knockdown in mouse excitatory neurons interferes with dendrite arborization and spine maturation which could not be rescued by de novo missense variants identified from affected individuals. In summary, our findings suggest that PSDVs may play an important role in the genetic etiology of ASD and allow for the prioritization of new ASD candidate genes. Importantly, we show that genetic variation resulting in GSK3B loss-of-function can lead to a neurodevelopmental disorder with core features of ASD and developmental delay.De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de novo potential splicing-disrupting variants (PSDVs) in 5048 probands compared to 4090 unaffected siblings. We identified 55 genes with recurrent de novo PSDVs that were highly intolerant to variation. Forty-six of these genes have not been strongly implicated in ASD or other neurodevelopmental disorders previously, including GSK3B. Through international, multicenter collaborations, we assembled genotype and phenotype data for 15 individuals with GSK3B variants and identified common phenotypes including developmental delay, ASD, sleeping disturbance, and aggressive behavior. Using available single-cell transcriptomic data, we show that GSK3B is enriched in dorsal progenitors and intermediate forms of excitatory neurons in the developing brain. We showed that Gsk3b knockdown in mouse excitatory neurons interferes with dendrite arborization and spine maturation which could not be rescued by de novo missense variants identified from affected individuals. In summary, our findings suggest that PSDVs may play an important role in the genetic etiology of ASD and allow for the prioritization of new ASD candidate genes. Importantly, we show that genetic variation resulting in GSK3B loss-of-function can lead to a neurodevelopmental disorder with core features of ASD and developmental delay. De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de novo potential splicing-disrupting variants (PSDVs) in 5048 probands compared to 4090 unaffected siblings. We identified 55 genes with recurrent de novo PSDVs that were highly intolerant to variation. Forty-six of these genes have not been strongly implicated in ASD or other neurodevelopmental disorders previously, including GSK3B . Through international, multicenter collaborations, we assembled genotype and phenotype data for 15 individuals with GSK3B variants and identified common phenotypes including developmental delay, ASD, sleeping disturbance, and aggressive behavior. Using available single-cell transcriptomic data, we show that GSK3B is enriched in dorsal progenitors and intermediate forms of excitatory neurons in the developing brain. We showed that Gsk3b knockdown in mouse excitatory neurons interferes with dendrite arborization and spine maturation which could not be rescued by de novo missense variants identified from affected individuals. In summary, our findings suggest that PSDVs may play an important role in the genetic etiology of ASD and allow for the prioritization of new ASD candidate genes. Importantly, we show that genetic variation resulting in GSK3B loss-of-function can lead to a neurodevelopmental disorder with core features of ASD and developmental delay. De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de novo potential splicing-disrupting variants (PSDVs) in 5048 probands compared to 4090 unaffected siblings. We identified 55 genes with recurrent de novo PSDVs that were highly intolerant to variation. Forty-six of these genes have not been strongly implicated in ASD or other neurodevelopmental disorders previously, including GSK3B. Through international, multicenter collaborations, we assembled genotype and phenotype data for 15 individuals with GSK3B variants and identified common phenotypes including developmental delay, ASD, sleeping disturbance, and aggressive behavior. Using available single-cell transcriptomic data, we show that GSK3B is enriched in dorsal progenitors and intermediate forms of excitatory neurons in the developing brain. We showed that Gsk3b knockdown in mouse excitatory neurons interferes with dendrite arborization and spine maturation which could not be rescued by de novo missense variants identified from affected individuals. In summary, our findings suggest that PSDVs may play an important role in the genetic etiology of ASD and allow for the prioritization of new ASD candidate genes. Importantly, we show that genetic variation resulting in GSK3B loss-of-function can lead to a neurodevelopmental disorder with core features of ASD and developmental delay. |
Author | Han, Yaoling Kreiß, Martina Morrow, Michelle M. Pingault, Veronique Racine, Caroline Li, Xing Besterman, Aaron D. Leahy, Peter Tran-Mau-Them, Frederic Madden, Jill A. Tan, Jieqiong Xia, Kun Spataro, Nino Yu, Bin Martinez, Julian Urion, David K. Peters, Sophia Marlin, Sandrine Begtrup, Amber Hu, Zhengmao Zhan, Rui Luo, Si Wang, Xiuxia Zhou, Shimin Trujillo-Quintero, Juan Pablo Zhang, Qiumeng Perne, Claudia Li, Faxiang Jurgensmeyer, Sarah Tan, Senwei Muss, Candace Delahaye, Andrée Guo, Hui Srivastava, Siddharth Saif, Hind Al Phornphutkul, Chanika Tian, Xiaoyu |
Author_xml | – sequence: 1 givenname: Senwei surname: Tan fullname: Tan, Senwei organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University – sequence: 2 givenname: Qiumeng surname: Zhang fullname: Zhang, Qiumeng organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University – sequence: 3 givenname: Rui surname: Zhan fullname: Zhan, Rui organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University – sequence: 4 givenname: Si surname: Luo fullname: Luo, Si organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University – sequence: 5 givenname: Yaoling surname: Han fullname: Han, Yaoling organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University – sequence: 6 givenname: Bin surname: Yu fullname: Yu, Bin organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University – sequence: 7 givenname: Candace surname: Muss fullname: Muss, Candace organization: Department of Genetics, Nemours Children’s Hospital – sequence: 8 givenname: Veronique surname: Pingault fullname: Pingault, Veronique organization: Service de Médecine Génomique des maladies rares, AP-HP, Hôpital Necker; Université Paris Cité, Inserm, Institut Imagine; and Laboratoire de Biologie Médicale Multi-Sites SeqOIA – sequence: 9 givenname: Sandrine surname: Marlin fullname: Marlin, Sandrine organization: Centre de Référence «Surdités Génétiques», Fédération de Génétique; Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Laboratory of Embryology and Genetics of Malformations, Imagine Institute, INSERM UMR 1163, Université de Paris – sequence: 10 givenname: Andrée orcidid: 0000-0003-4324-7372 surname: Delahaye fullname: Delahaye, Andrée organization: Service de Médecine Génomique des maladies rares, AP-HP, Hôpital Necker; Université Paris Cité, Inserm, Institut Imagine; and Laboratoire de Biologie Médicale Multi-Sites SeqOIA – sequence: 11 givenname: Sophia surname: Peters fullname: Peters, Sophia organization: Institute of Human Genetics, School of Medicine, University Hospital Bonn, University of Bonn – sequence: 12 givenname: Claudia surname: Perne fullname: Perne, Claudia organization: Institute of Human Genetics, School of Medicine, University Hospital Bonn, University of Bonn – sequence: 13 givenname: Martina surname: Kreiß fullname: Kreiß, Martina organization: Institute of Human Genetics, School of Medicine, University Hospital Bonn, University of Bonn – sequence: 14 givenname: Nino surname: Spataro fullname: Spataro, Nino organization: Center for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona – sequence: 15 givenname: Juan Pablo surname: Trujillo-Quintero fullname: Trujillo-Quintero, Juan Pablo organization: Center for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona – sequence: 16 givenname: Caroline orcidid: 0000-0003-2378-5982 surname: Racine fullname: Racine, Caroline organization: Unité Fonctionnelle d’Innovation diagnostique des maladies rares, FHU-TRANSLAD, CHU Dijon Bourgogne – sequence: 17 givenname: Frederic surname: Tran-Mau-Them fullname: Tran-Mau-Them, Frederic organization: Unité Fonctionnelle d’Innovation diagnostique des maladies rares, FHU-TRANSLAD, CHU Dijon Bourgogne – sequence: 18 givenname: Chanika surname: Phornphutkul fullname: Phornphutkul, Chanika organization: Division of Human Genetics, Department of Pediatrics, Warren Alpert Medical School of Brown University, Hasbro Children’s Hospital – sequence: 19 givenname: Aaron D. orcidid: 0000-0002-8671-1203 surname: Besterman fullname: Besterman, Aaron D. organization: Department of Psychiatry, University of California San Diego School of Medicine, Rady Children’s Hospital, Rady Children’s Institute for Genomic Medicine – sequence: 20 givenname: Julian surname: Martinez fullname: Martinez, Julian organization: Departments of Human Genetics, Pediatrics and Psychiatry, David Geffen School of Medicine, University of California Los Angeles – sequence: 21 givenname: Xiuxia surname: Wang fullname: Wang, Xiuxia organization: Department of Pediatrics, The Second Hospital of Hebei Medical University – sequence: 22 givenname: Xiaoyu surname: Tian fullname: Tian, Xiaoyu organization: Department of Pediatrics, The Second Hospital of Hebei Medical University – sequence: 23 givenname: Siddharth surname: Srivastava fullname: Srivastava, Siddharth organization: Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Harvard University – sequence: 24 givenname: David K. surname: Urion fullname: Urion, David K. organization: Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Harvard University – sequence: 25 givenname: Jill A. surname: Madden fullname: Madden, Jill A. organization: Division of Genetics and Genomics, Boston Children’s Hospital, The Manton Center for Orphan Disease Research, Boston Children’s Hospital – sequence: 26 givenname: Hind Al surname: Saif fullname: Saif, Hind Al organization: Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Virginia Commonwealth – sequence: 27 givenname: Michelle M. surname: Morrow fullname: Morrow, Michelle M. organization: GeneDx – sequence: 28 givenname: Amber orcidid: 0000-0002-2872-3281 surname: Begtrup fullname: Begtrup, Amber organization: GeneDx – sequence: 29 givenname: Xing surname: Li fullname: Li, Xing organization: Departments of Pediatrics, The First Affiliated Hospital of Guangxi Medical University – sequence: 30 givenname: Sarah orcidid: 0000-0002-0361-6367 surname: Jurgensmeyer fullname: Jurgensmeyer, Sarah organization: Division of Genetics, Genomics and Metabolism, Ann & Robert H. Lurie Children’s Hospital of Chicago, Department of Pediatrics, Northwestern University Feinberg School of Medicine – sequence: 31 givenname: Peter surname: Leahy fullname: Leahy, Peter organization: Division of Genetics, Genomics and Metabolism, Ann & Robert H. Lurie Children’s Hospital of Chicago, Department of Pediatrics, Northwestern University Feinberg School of Medicine – sequence: 32 givenname: Shimin surname: Zhou fullname: Zhou, Shimin organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University – sequence: 33 givenname: Faxiang surname: Li fullname: Li, Faxiang organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University – sequence: 34 givenname: Zhengmao surname: Hu fullname: Hu, Zhengmao organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University – sequence: 35 givenname: Jieqiong surname: Tan fullname: Tan, Jieqiong organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University – sequence: 36 givenname: Kun orcidid: 0000-0001-8090-6002 surname: Xia fullname: Xia, Kun email: xiakun@sklmg.edu.cn organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University, MOE Key Lab of Rare Pediatric Diseases, School of Basic Medicine, Hengyang Medical College, University of South China, Furong Laboratory – sequence: 37 givenname: Hui orcidid: 0000-0002-1570-2545 surname: Guo fullname: Guo, Hui email: guohui@sklmg.edu.cn organization: Center for Medical Genetics & MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University, Furong Laboratory |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/39472663$$D View this record in MEDLINE/PubMed |
BookMark | eNp9kU9PHSEUxUljU_-0X8CFIXHjhha4MMMsq7FqatNF65rwGMZgGHgFxkQ_vbw-jYkLQwj3ht-5uTlnH-3EFB1Ch4x-ZRTUtyIYKEooF-0q2pHHD2iPib4jUvZqp9UgByKYErtov5Q7Sjef8hPahUH0vOtgD938SjGZEFzwFodUCkkTmZZoq08R35vsTawF-4gv_vyEUxycGXFN2CzVlxmbOOLR3buQ1rOL1YTWBfPwGX2cTCjuy_N7gG5-nP89uyTXvy-uzr5fEwu9rGToGDUrwYeeKyGUs1Rwzkdg1hpunFrJ1aDoBK1mE-UTSJiMbZRzg1RUwQE62c5d5_RvcaXq2RfrQjDRpaVoYJx30E7f0OM36F1acmzbaeAMetZTCY06eqaW1exGvc5-NvlBvxjWALUFbG5mZTdp66vZmFWz8UEzqjfZ6G02umWj_2ejH5uUv5G-TH9XBFtRaXC8dfl17XdUT5o2oCk |
CitedBy_id | crossref_primary_10_53053_LWRF1005 |
Cites_doi | 10.1038/nprot.2012.099 10.1016/j.bbamcr.2020.118664 10.3233/JAD-2012-129025 10.1016/j.lfs.2009.09.009 10.1016/j.ridd.2009.06.003 10.1038/ng.3050 10.1038/nature08250 10.1038/nbt.4314 10.1093/nar/gkac1000 10.1016/j.tcm.2007.01.004 10.1093/nar/gkq603 10.3390/life12050648 10.1038/nature13772 10.1016/j.ejmg.2016.11.008 10.1002/jcp.30290 10.1016/S2215-0366(19)30289-5 10.1093/nar/gkg509 10.1016/j.neuron.2018.01.015 10.1016/j.cell.2019.07.015 10.1503/jpn.200185 10.1038/s41572-019-0138-4 10.1016/j.cell.2022.10.009 10.1007/s00439-017-1783-x 10.1001/jama.2022.23661 10.1016/j.biopsych.2018.02.1173 10.1186/s13059-016-0974-4 10.1002/jbmr.266 10.1038/s41586-020-2832-5 10.1016/j.phrs.2015.03.010 10.1093/brain/awx054 10.1093/bioinformatics/btab503 10.1517/14728222.9.3.447 10.1016/j.cell.2019.12.036 10.1038/nature13908 10.1038/nrg.2016.46 10.1038/s41588-022-01148-2 10.1186/s13073-022-01042-w 10.1016/j.cell.2018.12.015 10.1016/j.neuron.2016.02.024 10.1016/j.tig.2022.03.009 10.1038/ng.3303 10.1038/s41594-022-00844-1 10.1002/humu.22932 10.1038/s41588-022-01104-0 10.1038/nature13185 10.1126/science.aat6576 10.1016/S0092-8674(02)00685-2 10.1038/s41588-021-00899-8 10.1038/nmeth.4402 10.1101/gr.238444.118 10.1371/journal.pgen.1003671 10.1002/sctm.17-0229 10.1038/s41588-018-0288-4 10.1016/j.gim.2022.08.006 10.1016/S0140-6736(18)31129-2 10.1073/pnas.2203491119 10.1016/j.tibs.2009.10.002 10.1002/pro.4218 10.1016/j.biopsych.2010.11.015 10.1186/s13073-021-00835-9 10.1161/01.RES.0000018952.70505.F1 10.1038/nmeth0410-248 10.1016/j.biopha.2018.11.103 10.1016/j.ajhg.2012.02.007 10.1002/humu.22844 10.1038/s41586-020-2308-7 10.1016/j.brainres.2008.11.057 10.1038/nbt.2859 10.1038/nn.4524 10.1126/science.1227764 10.1186/gb-2005-6-5-r44 10.1186/s13073-023-01261-9 |
ContentType | Journal Article |
Copyright | The Author(s), under exclusive licence to Springer Nature Limited 2024 Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. 2024. The Author(s), under exclusive licence to Springer Nature Limited. Copyright Nature Publishing Group May 2025 |
Copyright_xml | – notice: The Author(s), under exclusive licence to Springer Nature Limited 2024 Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. – notice: 2024. The Author(s), under exclusive licence to Springer Nature Limited. – notice: Copyright Nature Publishing Group May 2025 |
DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7TK K9. 7X8 |
DOI | 10.1038/s41380-024-02806-z |
DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Neurosciences Abstracts ProQuest Health & Medical Complete (Alumni) MEDLINE - Academic |
DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) ProQuest Health & Medical Complete (Alumni) Neurosciences Abstracts MEDLINE - Academic |
DatabaseTitleList | MEDLINE - Academic ProQuest Health & Medical Complete (Alumni) MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine Biology |
EISSN | 1476-5578 |
EndPage | 1965 |
ExternalDocumentID | 39472663 10_1038_s41380_024_02806_z |
Genre | Journal Article |
GrantInformation_xml | – fundername: National Natural Science Foundation of China (National Science Foundation of China) grantid: 2021ZD0201704 funderid: https://doi.org/10.13039/501100001809 – fundername: National Natural Science Foundation of China (National Science Foundation of China) grantid: 2021ZD0201704 |
GroupedDBID | --- -Q- 0R~ 123 29M 2WC 36B 39C 4.4 406 53G 70F 7X7 88E 8AO 8FI 8FJ 8R4 8R5 AACDK AANZL AASML AATNV AAYZH ABAKF ABAWZ ABBRH ABDBE ABDBF ABIVO ABJNI ABLJU ABUWG ABZZP ACAOD ACGFS ACKTT ACPRK ACRQY ACUHS ACZOJ ADBBV AEFQL AEJRE AEMSY AENEX AEVLU AEXYK AFBBN AFDZB AFKRA AFRAH AFSHS AGAYW AGHAI AGQEE AHMBA AHSBF AIGIU AILAN AJRNO ALFFA ALIPV ALMA_UNASSIGNED_HOLDINGS AMYLF AXYYD AYFIA AZQEC B0M BAWUL BBNVY BENPR BHPHI BKKNO BPHCQ BVXVI CAG CCPQU COF CS3 DIK DNIVK DPUIP DU5 DWQXO E3Z EAD EAP EBC EBD EBLON EBS EE. EIOEI EJD EMB EMK EMOBN EPL EPS ESX F5P FDQFY FEDTE FERAY FIGPU FIZPM FSGXE FYUFA GNUQQ HCIFZ HMCUK HVGLF HZ~ IAO IHR INH INR IPY ITC IWAJR JSO JZLTJ KQ8 M1P M2M M7P NQJWS O9- OK1 OVD P2P PHGZT PQQKQ PROAC PSQYO PSYQQ Q2X RNS RNT RNTTT ROL SNX SNYQT SOHCF SOJ SRMVM SV3 SWTZT TAOOD TBHMF TDRGL TEORI TR2 TSG TUS UKHRP ~8M AAYXX ABFSG ABRTQ ACSTC AEZWR AFHIU AHWEU AIXLP ATHPR CITATION CGR CUY CVF ECM EIF NPM 7TK K9. 7X8 |
ID | FETCH-LOGICAL-c375t-9610ab429728448ec04222d31cca2ae8b5b980f32ae1f02f353facc04ee958083 |
ISSN | 1359-4184 1476-5578 |
IngestDate | Fri Sep 05 14:38:45 EDT 2025 Sat Aug 23 12:23:20 EDT 2025 Thu Apr 24 02:13:59 EDT 2025 Wed Oct 01 06:29:43 EDT 2025 Thu Apr 24 22:50:21 EDT 2025 Wed Apr 23 01:17:58 EDT 2025 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 5 |
Language | English |
License | 2024. The Author(s), under exclusive licence to Springer Nature Limited. |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c375t-9610ab429728448ec04222d31cca2ae8b5b980f32ae1f02f353facc04ee958083 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
ORCID | 0000-0002-8671-1203 0000-0003-4324-7372 0000-0003-2378-5982 0000-0002-0361-6367 0000-0001-8090-6002 0000-0002-1570-2545 0000-0002-2872-3281 |
PMID | 39472663 |
PQID | 3213717053 |
PQPubID | 44096 |
PageCount | 14 |
ParticipantIDs | proquest_miscellaneous_3122636367 proquest_journals_3213717053 pubmed_primary_39472663 crossref_citationtrail_10_1038_s41380_024_02806_z crossref_primary_10_1038_s41380_024_02806_z springer_journals_10_1038_s41380_024_02806_z |
ProviderPackageCode | CITATION AAYXX |
PublicationCentury | 2000 |
PublicationDate | 2025-05-01 |
PublicationDateYYYYMMDD | 2025-05-01 |
PublicationDate_xml | – month: 05 year: 2025 text: 2025-05-01 day: 01 |
PublicationDecade | 2020 |
PublicationPlace | London |
PublicationPlace_xml | – name: London – name: England – name: New York |
PublicationTitle | Molecular psychiatry |
PublicationTitleAbbrev | Mol Psychiatry |
PublicationTitleAlternate | Mol Psychiatry |
PublicationYear | 2025 |
Publisher | Nature Publishing Group UK Nature Publishing Group |
Publisher_xml | – name: Nature Publishing Group UK – name: Nature Publishing Group |
References | JA Miller (2806_CR49) 2014; 508 JM Fu (2806_CR10) 2022; 54 C Trapnell (2806_CR45) 2014; 32 S Deng (2806_CR61) 2019; 110 J Lord (2806_CR20) 2019; 29 2806_CR44 SB Ng (2806_CR25) 2009; 461 AJM Blakes (2806_CR39) 2022; 14 S Kayumi (2806_CR69) 2022; 24 A Khayachi (2806_CR66) 2021; 46 JL Matson (2806_CR5) 2009; 30 K Eilbeck (2806_CR18) 2005; 6 K Wang (2806_CR27) 2010; 38 J Kaplanis (2806_CR40) 2020; 586 K Hamanaka (2806_CR14) 2022; 14 J Cheng (2806_CR29) 2019; 20 K Jaganathan (2806_CR32) 2019; 176 FS Wang (2806_CR62) 2009; 85 B Trost (2806_CR8) 2022; 185 EK Ruzzo (2806_CR15) 2019; 178 BH Clough (2806_CR64) 2018; 7 KJ Karczewski (2806_CR48) 2020; 581 IA Adzhubei (2806_CR57) 2010; 7 N Krumm (2806_CR12) 2015; 47 X Zhou (2806_CR9) 2022; 54 ML Speir (2806_CR43) 2021; 37 X He (2806_CR37) 2013; 9 T Wang (2806_CR41) 2022; 119 RK C Yuen (2806_CR24) 2017; 20 BJ O’Roak (2806_CR36) 2012; 338 C Lord (2806_CR1) 2018; 392 A Takata (2806_CR19) 2016; 89 FK Satterstrom (2806_CR23) 2020; 180 T Wang (2806_CR11) 2022; 38 JS Ware (2806_CR35) 2015; 87 C Lord (2806_CR3) 2020; 6 M Golpich (2806_CR53) 2015; 97 D Stein (2806_CR38) 2023; 15 C Liu (2806_CR71) 2002; 108 D Wu (2806_CR68) 2010; 35 2806_CR22 I Iossifov (2806_CR7) 2014; 515 F Hernandez (2806_CR55) 2013; 33 CR Sibley (2806_CR16) 2016; 17 KE Samocha (2806_CR33) 2014; 46 PC Ng (2806_CR56) 2003; 31 HL Chiang (2806_CR17) 2022; 29 SE Hardt (2806_CR58) 2002; 90 J Li (2806_CR65) 2021; 236 E Murphy (2806_CR59) 2005; 9 BP Coe (2806_CR4) 2019; 51 S De Rubeis (2806_CR52) 2014; 515 R Kerkela (2806_CR60) 2007; 17 pfeliciano@simonsfoundation.org SCEa, Consortium S. (2806_CR21) 2018; 97 N Sobreira (2806_CR42) 2015; 36 FF Hamdan (2806_CR74) 2011; 69 E Lauretti (2806_CR54) 2020; 1867 MC Lai (2806_CR6) 2019; 6 M Wolff (2806_CR72) 2017; 140 2806_CR34 X Qiu (2806_CR46) 2017; 14 GMJ Beaudoin (2806_CR47) 2012; 7 X Liu (2806_CR31) 2016; 37 W McLaren (2806_CR26) 2016; 17 L Martin (2806_CR67) 2009; 1252 J Hoyer (2806_CR73) 2012; 90 A Van Dijck (2806_CR75) 2019; 85 M Kharbanda (2806_CR70) 2017; 60 P Rentzsch (2806_CR28) 2021; 13 T Hirota (2806_CR2) 2023; 329 AB Wilfert (2806_CR13) 2021; 53 PD Thomas (2806_CR51) 2022; 31 D Szklarczyk (2806_CR50) 2023; 51 X Zhang (2806_CR30) 2017; 136 A Gambardella (2806_CR63) 2011; 26 |
References_xml | – volume: 7 start-page: 1741 year: 2012 ident: 2806_CR47 publication-title: Nat Protoc doi: 10.1038/nprot.2012.099 – volume: 1867 year: 2020 ident: 2806_CR54 publication-title: Biochim Biophys Acta Mol Cell Res doi: 10.1016/j.bbamcr.2020.118664 – volume: 33 start-page: S141 year: 2013 ident: 2806_CR55 publication-title: J Alzheimers Dis doi: 10.3233/JAD-2012-129025 – volume: 85 start-page: 685 year: 2009 ident: 2806_CR62 publication-title: Life Sci doi: 10.1016/j.lfs.2009.09.009 – volume: 30 start-page: 1107 year: 2009 ident: 2806_CR5 publication-title: Res Dev Disabil doi: 10.1016/j.ridd.2009.06.003 – volume: 46 start-page: 944 year: 2014 ident: 2806_CR33 publication-title: Nat Genet doi: 10.1038/ng.3050 – volume: 461 start-page: 272 year: 2009 ident: 2806_CR25 publication-title: Nature doi: 10.1038/nature08250 – ident: 2806_CR44 doi: 10.1038/nbt.4314 – volume: 51 start-page: D638 year: 2023 ident: 2806_CR50 publication-title: Nucleic Acids Res doi: 10.1093/nar/gkac1000 – volume: 17 start-page: 91 year: 2007 ident: 2806_CR60 publication-title: Trends Cardiovasc Med doi: 10.1016/j.tcm.2007.01.004 – volume: 38 start-page: e164 year: 2010 ident: 2806_CR27 publication-title: Nucleic Acids Res doi: 10.1093/nar/gkq603 – ident: 2806_CR34 doi: 10.3390/life12050648 – volume: 515 start-page: 209 year: 2014 ident: 2806_CR52 publication-title: Nature doi: 10.1038/nature13772 – volume: 60 start-page: 130 year: 2017 ident: 2806_CR70 publication-title: Eur J Med Genet doi: 10.1016/j.ejmg.2016.11.008 – volume: 236 start-page: 6042 year: 2021 ident: 2806_CR65 publication-title: J Cell Physiol doi: 10.1002/jcp.30290 – volume: 6 start-page: 819 year: 2019 ident: 2806_CR6 publication-title: Lancet Psychiatry doi: 10.1016/S2215-0366(19)30289-5 – volume: 31 start-page: 3812 year: 2003 ident: 2806_CR56 publication-title: Nucleic Acids Res doi: 10.1093/nar/gkg509 – volume: 97 start-page: 488 year: 2018 ident: 2806_CR21 publication-title: Neuron doi: 10.1016/j.neuron.2018.01.015 – volume: 178 start-page: 850 year: 2019 ident: 2806_CR15 publication-title: Cell doi: 10.1016/j.cell.2019.07.015 – volume: 46 start-page: E402 year: 2021 ident: 2806_CR66 publication-title: J Psychiatry Neurosci doi: 10.1503/jpn.200185 – volume: 6 start-page: 5 year: 2020 ident: 2806_CR3 publication-title: Nat Rev Dis Primers doi: 10.1038/s41572-019-0138-4 – volume: 185 start-page: 4409 year: 2022 ident: 2806_CR8 publication-title: Cell doi: 10.1016/j.cell.2022.10.009 – volume: 136 start-page: 1279 year: 2017 ident: 2806_CR30 publication-title: Hum Genet doi: 10.1007/s00439-017-1783-x – volume: 329 start-page: 157 year: 2023 ident: 2806_CR2 publication-title: JAMA doi: 10.1001/jama.2022.23661 – volume: 85 start-page: 287 year: 2019 ident: 2806_CR75 publication-title: Biol Psychiatry doi: 10.1016/j.biopsych.2018.02.1173 – volume: 17 year: 2016 ident: 2806_CR26 publication-title: Genome Biol doi: 10.1186/s13059-016-0974-4 – volume: 26 start-page: 811 year: 2011 ident: 2806_CR63 publication-title: J Bone Miner Res doi: 10.1002/jbmr.266 – volume: 586 start-page: 757 year: 2020 ident: 2806_CR40 publication-title: Nature doi: 10.1038/s41586-020-2832-5 – volume: 97 start-page: 16 year: 2015 ident: 2806_CR53 publication-title: Pharmacol Res doi: 10.1016/j.phrs.2015.03.010 – volume: 140 start-page: 1316 year: 2017 ident: 2806_CR72 publication-title: Brain doi: 10.1093/brain/awx054 – volume: 37 start-page: 4578 year: 2021 ident: 2806_CR43 publication-title: Bioinformatics doi: 10.1093/bioinformatics/btab503 – volume: 9 start-page: 447 year: 2005 ident: 2806_CR59 publication-title: Expert Opin Ther Targets doi: 10.1517/14728222.9.3.447 – volume: 180 start-page: 568 year: 2020 ident: 2806_CR23 publication-title: Cell doi: 10.1016/j.cell.2019.12.036 – volume: 14 year: 2022 ident: 2806_CR39 publication-title: Genome Med – volume: 515 start-page: 216 year: 2014 ident: 2806_CR7 publication-title: Nature doi: 10.1038/nature13908 – volume: 17 start-page: 407 year: 2016 ident: 2806_CR16 publication-title: Nat Rev Genet doi: 10.1038/nrg.2016.46 – volume: 54 start-page: 1305 year: 2022 ident: 2806_CR9 publication-title: Nat Genet doi: 10.1038/s41588-022-01148-2 – volume: 14 year: 2022 ident: 2806_CR14 publication-title: Genome Med doi: 10.1186/s13073-022-01042-w – volume: 20 year: 2019 ident: 2806_CR29 publication-title: Genome Biol – volume: 176 start-page: 535 year: 2019 ident: 2806_CR32 publication-title: Cell doi: 10.1016/j.cell.2018.12.015 – volume: 89 start-page: 940 year: 2016 ident: 2806_CR19 publication-title: Neuron doi: 10.1016/j.neuron.2016.02.024 – volume: 38 start-page: 895 year: 2022 ident: 2806_CR11 publication-title: Trends Genet doi: 10.1016/j.tig.2022.03.009 – volume: 47 start-page: 582 year: 2015 ident: 2806_CR12 publication-title: Nat Genet doi: 10.1038/ng.3303 – volume: 29 start-page: 1043 year: 2022 ident: 2806_CR17 publication-title: Nat Struct Mol Biol doi: 10.1038/s41594-022-00844-1 – volume: 37 start-page: 235 year: 2016 ident: 2806_CR31 publication-title: Hum Mutat doi: 10.1002/humu.22932 – volume: 54 start-page: 1320 year: 2022 ident: 2806_CR10 publication-title: Nat Genet doi: 10.1038/s41588-022-01104-0 – volume: 508 start-page: 199 year: 2014 ident: 2806_CR49 publication-title: Nature doi: 10.1038/nature13185 – ident: 2806_CR22 doi: 10.1126/science.aat6576 – volume: 108 start-page: 837 year: 2002 ident: 2806_CR71 publication-title: Cell doi: 10.1016/S0092-8674(02)00685-2 – volume: 53 start-page: 1125 year: 2021 ident: 2806_CR13 publication-title: Nat Genet doi: 10.1038/s41588-021-00899-8 – volume: 14 start-page: 979 year: 2017 ident: 2806_CR46 publication-title: Nat Methods doi: 10.1038/nmeth.4402 – volume: 87 start-page: 7 year: 2015 ident: 2806_CR35 publication-title: Curr Protoc Hum Genet – volume: 29 start-page: 159 year: 2019 ident: 2806_CR20 publication-title: Genome Res doi: 10.1101/gr.238444.118 – volume: 9 start-page: e1003671 year: 2013 ident: 2806_CR37 publication-title: PLoS Genet doi: 10.1371/journal.pgen.1003671 – volume: 7 start-page: 342 year: 2018 ident: 2806_CR64 publication-title: Stem Cells Transl Med doi: 10.1002/sctm.17-0229 – volume: 51 start-page: 106 year: 2019 ident: 2806_CR4 publication-title: Nat Genet doi: 10.1038/s41588-018-0288-4 – volume: 24 start-page: 2351 year: 2022 ident: 2806_CR69 publication-title: Genet Med doi: 10.1016/j.gim.2022.08.006 – volume: 392 start-page: 508 year: 2018 ident: 2806_CR1 publication-title: Lancet doi: 10.1016/S0140-6736(18)31129-2 – volume: 119 start-page: e2203491119 year: 2022 ident: 2806_CR41 publication-title: Proc Natl Acad Sci USA doi: 10.1073/pnas.2203491119 – volume: 35 start-page: 161 year: 2010 ident: 2806_CR68 publication-title: Trends Biochem Sci doi: 10.1016/j.tibs.2009.10.002 – volume: 31 start-page: 8 year: 2022 ident: 2806_CR51 publication-title: Protein Sci doi: 10.1002/pro.4218 – volume: 69 start-page: 898 year: 2011 ident: 2806_CR74 publication-title: Biol Psychiatry doi: 10.1016/j.biopsych.2010.11.015 – volume: 13 year: 2021 ident: 2806_CR28 publication-title: Genome Med doi: 10.1186/s13073-021-00835-9 – volume: 90 start-page: 1055 year: 2002 ident: 2806_CR58 publication-title: Circ Res doi: 10.1161/01.RES.0000018952.70505.F1 – volume: 7 start-page: 248 year: 2010 ident: 2806_CR57 publication-title: Nat Methods doi: 10.1038/nmeth0410-248 – volume: 110 start-page: 602 year: 2019 ident: 2806_CR61 publication-title: Biomed Pharmacother doi: 10.1016/j.biopha.2018.11.103 – volume: 90 start-page: 565 year: 2012 ident: 2806_CR73 publication-title: Am J Hum Genet doi: 10.1016/j.ajhg.2012.02.007 – volume: 36 start-page: 928 year: 2015 ident: 2806_CR42 publication-title: Hum Mutat doi: 10.1002/humu.22844 – volume: 581 start-page: 434 year: 2020 ident: 2806_CR48 publication-title: Nature doi: 10.1038/s41586-020-2308-7 – volume: 1252 start-page: 66 year: 2009 ident: 2806_CR67 publication-title: Brain Res doi: 10.1016/j.brainres.2008.11.057 – volume: 32 start-page: 381 year: 2014 ident: 2806_CR45 publication-title: Nat Biotechnol doi: 10.1038/nbt.2859 – volume: 20 start-page: 602 year: 2017 ident: 2806_CR24 publication-title: Nat Neurosci doi: 10.1038/nn.4524 – volume: 338 start-page: 1619 year: 2012 ident: 2806_CR36 publication-title: Science doi: 10.1126/science.1227764 – volume: 6 year: 2005 ident: 2806_CR18 publication-title: Genome Biol doi: 10.1186/gb-2005-6-5-r44 – volume: 15 year: 2023 ident: 2806_CR38 publication-title: Genome Med doi: 10.1186/s13073-023-01261-9 |
SSID | ssj0014765 |
Score | 2.4810996 |
Snippet | De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain... |
SourceID | proquest pubmed crossref springer |
SourceType | Aggregation Database Index Database Enrichment Source Publisher |
StartPage | 1952 |
SubjectTerms | 13/1 13/109 14/35 14/63 45/44 45/77 631/208 692/699/476/1373 Alleles Animals Autism Autism Spectrum Disorder - genetics Autistic Disorder - genetics Behavioral Sciences Biological Psychology Brain - metabolism Child Child, Preschool Dendritic spines Developmental Disabilities - genetics Female Genetic diversity Genetic Predisposition to Disease - genetics Genotypes Glycogen Synthase Kinase 3 beta - genetics Glycogen Synthase Kinase 3 beta - metabolism Humans Loss of Function Mutation - genetics Male Medicine Medicine & Public Health Mice Neurodevelopmental disorders Neurons - metabolism Neurosciences Pharmacotherapy Phenotype Phenotypes Psychiatry Splicing Transcriptomics Whole genome sequencing |
Title | Monoallelic loss-of-function variants in GSK3B lead to autism and developmental delay |
URI | https://link.springer.com/article/10.1038/s41380-024-02806-z https://www.ncbi.nlm.nih.gov/pubmed/39472663 https://www.proquest.com/docview/3213717053 https://www.proquest.com/docview/3122636367 |
Volume | 30 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
journalDatabaseRights | – providerCode: PRVAFT databaseName: Open Access Digital Library customDbUrl: eissn: 1476-5578 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0014765 issn: 1359-4184 databaseCode: KQ8 dateStart: 19970101 isFulltext: true titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html providerName: Colorado Alliance of Research Libraries – providerCode: PRVLSH databaseName: SpringerLink Journals customDbUrl: mediaType: online eissn: 1476-5578 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014765 issn: 1359-4184 databaseCode: AFBBN dateStart: 19970101 isFulltext: true providerName: Library Specific Holdings |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnR1db9Mw0CqdQLwgGF-FgYzEW_Fo4jh2HlfEmBidhLZKe4vyYUuRqgSxBETf-d-cP_LRdkMMVYoS9-y4vfPd-e58h9BbnqoZ9_OMKD8KiLYxkChn8JiHQtGEBmmizzsvzsKTZfD5kl2ORr8HUUtNnR5m62vPlfwPVqEN8KpPyd4Cs92g0AD3gF-4Aobh-k84hgVZ6VooOlH1CqQdqRTRgsrg9Afsgk2QS1FOP52f0rmuEJFrXTOBKbnSGHkfM6S9NXKVbLh5F23x3K2oaLvXt6ZTWf6UxY79-WsBTM9JRddusNl0oF8aY6U9L4aGB5_1YX5t3m7t4ti2lk2XpwN2Spn2M9sicIfStgU8JIzZwj0tD3a-mWLo5TYM1YtsglsnnHX-w2sZv03zfgUiWcwI6B3EuIzJuhdzXfChcbtTEVvgGIBjAxyv76A9n4ehP0Z7R8fz-VnnjoIpM7Nzdz_Hnb6CUd7vvnJTw9nZtuy43I0mc_EQPXBbEHxk6ekRGslyH921RUl_7aN7Cxdu8RgtBwSGtwkMtwSGixIbAsOawHBdYUtgGAgMbxAYNgT2BC2PP158OCGuDgfJKGc1iUDFTlJQXDjoMoGQmc4b5-fUg9XvJ1KkLI3ETFG499TMV5RRlWQAJWXEBOj4T9G4rEr5HGGRhhz6iTBnNBAhS0SWeV7KuUpklqdqgrz2v4szl6Re10pZxTdjbYKmXZ9vNkXLX6EPWpTEbilfxdT3KNeJpegEvem-BkarvWdJKasGYDzYqVD48Al6ZlHZvY5GAQdNF3q_a3HbD37zXF7cDvwlut-vwwM0rr838hWoxHX62hHsHxNCsKw |
linkProvider | Library Specific Holdings |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Monoallelic+loss-of-function+variants+in+GSK3B+lead+to+autism+and+developmental+delay&rft.jtitle=Molecular+psychiatry&rft.au=Tan%2C+Senwei&rft.au=Zhang%2C+Qiumeng&rft.au=Zhan%2C+Rui&rft.au=Luo%2C+Si&rft.date=2025-05-01&rft.pub=Nature+Publishing+Group+UK&rft.issn=1359-4184&rft.eissn=1476-5578&rft.volume=30&rft.issue=5&rft.spage=1952&rft.epage=1965&rft_id=info:doi/10.1038%2Fs41380-024-02806-z&rft.externalDocID=10_1038_s41380_024_02806_z |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1359-4184&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1359-4184&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1359-4184&client=summon |