ArticleAmerican journal of human genetics2016
De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome.
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Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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68citing papers in PubMed
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68 citing papers in PubMed, 112 citations in OpenAlex.
- dsRNAscan maps human dsRNAome, revealing conservation, intermolecular dsRNA, and correlates of ADAR dependency.Molecular cell · 2026Article
- Nuclear speckles: a fundamental layer of gene regulation.Trends in cell biology · 2026Review
- Neurabin I haploinsufficiency disrupts ion channel regulation and synaptic maturation in human cortical neurons in neurodevelopmental disorders.Molecular psychiatry · 2026Article
- Targeting Osteoporosis-Osteoarthritis Comorbidity: Multi-Omics Identification of SON and Exploration of Therapeutic Agents.International journal of molecular sciences · 2026Article
- Captopril restores microglial homeostasis and reverses ASD-like phenotype in a model of ASD induced by exposure in utero to anti-caspr2 IgG.Molecular psychiatry · 2026Article
- ZTTK Syndrome Expanding the Cardiac Phenotype: A Case of Shone's Complex With a NovelCase reports in genetics · 2026Article
- Mid-gestational cell-type-specific transcriptomic signatures in the prefrontal and superior temporal cortex in Down syndrome.Nature communications · 2025Article
- Article
- CTCF/RAD21 organize the ground state of chromatin-nuclear speckle association.Nature structural & molecular biology · 2025Article
- Biological pathways leading to septo-optic dysplasia: a review.Orphanet journal of rare diseases · 2025Review
- [Zhu-Tokita-Takenouchi-Kim syndrome in a neonate].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Article
- SON is an essential RNA splicing factor promoting ErbB2 and ErbB3 expression in breast cancer.British journal of cancer · 2024Article
- Application of Whole-Exome Sequencing in the Prenatal Diagnosis of Foetuses With Central Nervous System Abnormalities.Molecular genetics & genomic medicine · 2024Article
- Splicing regulation through biomolecular condensates and membraneless organelles.Nature reviews. Molecular cell biology · 2024Review
- Optical genome mapping unveils hidden structural variants in neurodevelopmental disorders.Scientific reports · 2024Article
- Recurrent myocardial injury in a de novo SON mutation ZTTK syndrome patient: a case report.BMC pediatrics · 2024Article
- Nuclear speckleopathies: developmental disorders caused by variants in genes encoding nuclear speckle proteins.Human genetics · 2024Review
- A mouse model of Zhu-Tokita-Takenouchi-Kim syndrome reveals indispensable SON functions in organ development and hematopoiesis.JCI insight · 2024Article
- Diagnostic utility of exome sequencing followed by research reanalysis in human brain malformations.Brain communications · 2024Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
66 authors at 20 institutions in 6 countries.
Jung-Hyun KimMitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
Deepali N ShindeAmbry Genetics, Aliso Viejo, CA 92656, USA.
Margot R F ReijndersDepartment of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Natalie S HauserMedical Genetics and Metabolism, Valley Children's Hospital, Madera, CA 93636, USA.
Rebecca L BelmonteDepartment of Biological Sciences, California State University, Chico, Chico, CA 95929, USA.
Gregory R WilsonDepartment of Biological Sciences, California State University, Chico, Chico, CA 95929, USA.
Daniëlle G M BoschDepartment of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Paula A BubulyaDepartment of Biological Sciences, Wright State University, Dayton, OH 45435, USA.
Vandana ShashiDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Slavé PetrovskiDepartment of Medicine, University of Melbourne, Austin Hospital and Royal Melbourne Hospital, Parkville, VIC 3010, Australia; Institute for Genomic Medicine, Columbia University, New York, NY 10027, USA.
Joshua K StoneMitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
Eun Young ParkMitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
Joris A VeltmanDepartment of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Department of Clinical Genetics and School for Oncology & Developmental Biology (GROW), Maastricht University Medical Center, 6202 AZ Maastricht, the Netherlands.
Margje SinnemaDepartment of Clinical Genetics and School for Oncology & Developmental Biology (GROW), Maastricht University Medical Center, 6202 AZ Maastricht, the Netherlands.
Connie T R M StumpelDepartment of Clinical Genetics and School for Oncology & Developmental Biology (GROW), Maastricht University Medical Center, 6202 AZ Maastricht, the Netherlands.
Jos M DraaismaDepartment of Pediatrics, Radboudumc Amalia Children's Hospital, 6500 HB Nijmegen, the Netherlands.
Joost NicolaiDepartment of Neurology, Maastricht University Medical Center, 6299 HX Maastricht, the Netherlands.
University of Washington Center for Mendelian Genomics
Helger G YntemaDepartment of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Kristin LindstromDivision of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
Bert B A de VriesDepartment of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Tamison JewettSection on Medical Genetics, Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Stephanie L SantoroNationwide Children's Hospital, Columbus, OH 43205, USA; Ohio State University College of Medicine, Columbus, OH 43210, USA.
Julie VogtWest Midlands Regional Genetics Service, Birmingham Women's NHS Foundation Trust, Birmingham B15 2TG, UK.
Deciphering Developmental Disorders StudyWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Kristine K BachmanGeisinger Medical Center, Danville, PA 17822, USA.
Andrea H SeeleyGeisinger Medical Center, Danville, PA 17822, USA.
Alyson KrokoskyDivision of Genetics, Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, MD 20889, USA.
Clesson TurnerDivision of Genetics, Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, MD 20889, USA.
Luis RohenaDivision of Genetics, Department of Pediatrics, San Antonio Military Medical Center, Fort Sam Houston, TX 78234, USA; Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Maja HempelInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Fanny KortümInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Davor LesselInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Axel NeuDepartment of Pediatrics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Tim M StromInstitute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Human Genetics, Technical University of Munich, 81675 Munich, Germany.
Dagmar WieczorekInstitute of Human Genetics, University Clinic Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany; Institute of Human Genetics, University Clinic Essen, University Duisburg-Essen, 45147 Essen, Germany.
Nuria BramswigInstitute of Human Genetics, University Clinic Essen, University Duisburg-Essen, 45147 Essen, Germany.
Franco A LacconeInstitute of Medical Genetics, Medical University of Vienna, Waehringer Strasse 10, 1090 Vienna, Austria.
Jana BehunovaInstitute of Medical Genetics, Medical University of Vienna, Waehringer Strasse 10, 1090 Vienna, Austria.
Helga RehderInstitute of Medical Genetics, Medical University of Vienna, Waehringer Strasse 10, 1090 Vienna, Austria.
Christopher T GordonLaboratory of Embryology and Genetics of Congenital Malformations, INSERM UMR 1163, Institut Imagine, 75015 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.
Marlène RioDépartement de Génétique, Hôpital Necker-Enfants Malades, 75015 Paris, France.
Serge RomanaService de Cytogénétique, Hôpital Necker-Enfants Malades, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Institut Imagine, 75015 Paris, France.
Sha TangAmbry Genetics, Aliso Viejo, CA 92656, USA.
Dima El-KhechenAmbry Genetics, Aliso Viejo, CA 92656, USA.
Megan T ChoGeneDx Inc., 205 Perry Parkway, Gaithersburg, MD 20877, USA.
Kirsty McWalterGeneDx Inc., 205 Perry Parkway, Gaithersburg, MD 20877, USA.
Ganka DouglasGeneDx Inc., 205 Perry Parkway, Gaithersburg, MD 20877, USA.
Berivan BaskinGeneDx Inc., 205 Perry Parkway, Gaithersburg, MD 20877, USA.
Amber BegtrupGeneDx Inc., 205 Perry Parkway, Gaithersburg, MD 20877, USA.
Tara FunariGeneDx Inc., 205 Perry Parkway, Gaithersburg, MD 20877, USA.
Kelly SchochDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Alexander P A StegmannDepartment of Clinical Genetics and School for Oncology & Developmental Biology (GROW), Maastricht University Medical Center, 6202 AZ Maastricht, the Netherlands.
Servi J C StevensDepartment of Clinical Genetics and School for Oncology & Developmental Biology (GROW), Maastricht University Medical Center, 6202 AZ Maastricht, the Netherlands.
Dong-Er ZhangMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
David TraverDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Xu YaoMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Daniel G MacArthurBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Han G BrunnerDepartment of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Department of Clinical Genetics and School for Oncology & Developmental Biology (GROW), Maastricht University Medical Center, 6202 AZ Maastricht, the Netherlands.
Grazia M ManciniDepartment of Clinical Genetics, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands.
Richard M MyersHudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
Laurie B OwenMitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
Ssang-Taek LimDepartment of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.
David L StachuraDepartment of Biological Sciences, California State University, Chico, Chico, CA 95929, USA.
Lisenka E L M VissersDepartment of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands. Electronic address: lisenka.vissers@radboudumc.nl.
Eun-Young Erin AhnMitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA; Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA. Electronic address: eahn@health.southalabama.edu.
Genex Systems (United States) · USMaastricht University · NLRadboud University Nijmegen · NLAmbry Genetics (United States) · USCalifornia State University, Chico · USMedical University of Vienna · ATRadboud University Medical Center · NLUniversity of California, San Diego · USUniversity of South Alabama · USUSA Mitchell Cancer Institute · USDuke University · USGeisinger Medical Center · USHôpital Necker-Enfants Malades · FRUniversität Hamburg · DEUniversity Medical Center Hamburg-Eppendorf · DEUniversity of Duisburg-Essen · DEWalter Reed National Military Medical Center · USChildren's Hospital Central California · USColumbia University · USErasmus MC · NL
Funding
UW Center for Mendelian GenomicsU54HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, NICKERSON, DEBORAH A · 2012 to 2015
$20.0MUW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3MSON-mediated gene expression and leukemiaR01CA190688 · NCI · UNIVERSITY OF SOUTH ALABAMA · PI AHN, ERIN EUN-YOUNG · 2016 to 2021
$1.7MPre-mRNA Processing Factors Maintain Normal MitosisR15GM084407 · NIGMS · WRIGHT STATE UNIVERSITY · PI BUBULYA, PAULA A. · 2009 to 2019
$1.3MSON and the MALAT1 locus in chromatin interaction and metastasis gene regulationR21CA185818 · NCI · UNIVERSITY OF SOUTH ALABAMA · PI AHN, ERIN EUN-YOUNG · 2015 to 2016
$362kNCI NIH HHS R01 CA190688NCI NIH HHS R21 CA185818NHGRI NIH HHS U54 HG006493NHGRI NIH HHS UM1 HG006493NIGMS NIH HHS R15 GM084407Wellcome Trust
Abstract
The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development.
Indexed as
AnimalsBrainDevelopmental DisabilitiesDNA-Binding ProteinsEye AbnormalitiesFemaleGenes, EssentialHaploinsufficiencyHeadHeterozygoteHumansIntellectual DisabilityMaleMetabolic DiseasesMinor Histocompatibility AntigensMutationDNA-Binding ProteinsMinor Histocompatibility AntigensRNA, MessengerSON protein, human
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