ArticleAmerican journal of human genetics2024
MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway.
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Article in American journal of human genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12citing papers in PubMed
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Who cites it
12 citing papers in PubMed.
- Interpreting human genetic variation at atomic resolution.Nature genetics · 2026Review
- Loss-of-function variants in MARK2 cause neurodevelopmental disorder.HGG advances · 2026Article
- Pathophysiological roles of neural stem cells in neuropsychiatric diseases: from plasticity to pharmacological targeting.Acta pharmacologica Sinica · 2026Review
- Environmental context modulates sociability in ube3a zebrafish mutants via alterations in sensory pathways.Molecular psychiatry · 2026Article
- Case Report: Epileptic phenotype in a patient with aFrontiers in pediatrics · 2026Article
- Joint analysis ofNAR genomics and bioinformatics · 2025Article
- Beyond mTOR: Unraveling the Complex Pathophysiology and Signaling Pathways in Focal Cortical Dysplasia.Molecular neurobiology · 2025Review
- Article
- Emerging Epigenetic Therapeutics and Diagnostics for Autism Spectrum Disorder.Current issues in molecular biology · 2025Review
- Identification of a de Novo MARK2 gene variant in a patient with autism spectrum disorder, epilepsy, and neurodevelopmental delay.Neurogenetics · 2025Article
- Deleterious coding variation associated with autism is consistent across populations, as exemplified by admixed Latin American populations.medRxiv : the preprint server for health sciences · 2025Article
- Article
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Authors and funding
67 authors.
Maolei GongState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China; The Ninth Medical Center of PLA General Hospital, Beijing, China.
Jiayi LiDepartment of Medical Genetics, Capital Institute of Pediatrics, Beijing, China; Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Zailong QinGenetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
Matheus Vernet Machado Bressan WilkeDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Yijun LiuState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
Qian LiState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
Haoran LiuDepartment of Medical Genetics, Capital Institute of Pediatrics, Beijing, China.
Chen LiangDepartment of Medical Genetics, Capital Institute of Pediatrics, Beijing, China.
Joel A Morales-RosadoDepartment of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Ana S A CohenDepartment of Pathology and Laboratory Medicine, Genomic Medicine Center, Children's Mercy-Kansas City, Kansas City, MO, USA; The University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USA.
Susan S HughesThe University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USA; Division of Clinical Genetics, Children's Mercy Kansas City, Kansas City, MO, USA.
Bonnie R SullivanThe University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USA; Division of Clinical Genetics, Children's Mercy Kansas City, Kansas City, MO, USA.
Valerie WaddellDepartment of Neurology, Children's Mercy Kansas City, Kansas City, MO, USA.
Marie-José H van den BoogaardDepartment of Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Richard H van JaarsveldDepartment of Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Ellen van BinsbergenDepartment of Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Koen L van GassenDepartment of Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Tianyun WangDepartment of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Autism Research Center, Peking University Health Science Center, Beijing, China; Neuroscience Research Institute, Peking University, Key Laboratory for Neuroscience, Ministry of Education of China & National Health Commission of China, Beijing, China.
Susan M HiattHudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
Michelle D AmaralHudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
Whitley V KelleyHudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
Jianbo ZhaoDepartment of Neurology Beijing Children's Hospital, Capital Medical University, Beijing, China.
Weixing FengDepartment of Neurology Beijing Children's Hospital, Capital Medical University, Beijing, China.
Changhong RenDepartment of Neurology Beijing Children's Hospital, Capital Medical University, Beijing, China.
Yazhen YuDepartment of Pediatrics, Beijing Tiantan Hospital affiliated with Capital University of Medical Sciences, Beijing, China.
Nicole J BoczekDepartment of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN, USA.
Matthew J FerberDepartment of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN, USA.
Carrie LahnerDepartment of Laboratory Medicine and Pathology, Genomics Laboratory, Mayo Clinic, Rochester, MN, USA.
Sherr ElliottDepartments of Neurology and Pediatrics, Institute of Human Genetics and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Yiyan RuanGuangxi Clinical Research Center for Pediatric Diseases, The Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
Cyril MignotAPHP Sorbonne Université, Département de Génétique, Hôpital Pitié-Salpêtrière et Hôpital Trousseau, Centre de Référence Déficiences Intellectuelles de Causes Rares, Paris, France.
Boris KerenAPHP Sorbonne Université, Département de Génétique, Hôpital Pitié-Salpêtrière et Hôpital Trousseau, Centre de Référence Déficiences Intellectuelles de Causes Rares, Paris, France.
Hua XieDepartment of Medical Genetics, Capital Institute of Pediatrics, Beijing, China.
Xiaoyan WangDepartment of Children's Nutrition Research Center, Affiliated Children's Hospital of Capital Institute of Pediatrics, Beijing, China.
Bernt PoppInstitute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany; Berlin Institute of Health at Charité-Universitäts medizin Berlin, Center of Functional Genomics, Hessische Straße 4A, Berlin, Germany.
Christiane ZweierDepartment of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Juliette PiardCentre de Génétique Humaine, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France; UMR 1231 GAD, Inserm, Université de Bourgogne Franche Comté, Dijon, France.
Christine CoubesDépartement de Génétique Médicale, Maladies Rares et Médecine Personnalisée Hôpital Arnaud de Villeneuve, 34295 Montpellier Cedex, Dijon, France.
Frederic Tran Mau-ThemUF6254 Innovation en Diagnostic Genomique des Maladies Rares, Dijon, France; Inserm UMR1231 GAD, 21000 Dijon, France.
Hana SafraouUF6254 Innovation en Diagnostic Genomique des Maladies Rares, Dijon, France; Inserm UMR1231 GAD, 21000 Dijon, France.
A Micheil InnesDepartment of Medical Genetics and Pediatrics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Julie GauthierMolecular Diagnostic Laboratory, Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC, Canada; Department of Pediatrics, Université de Montréal, Montréal, QC, Canada.
Jacques L MichaudDepartment of Pediatrics, Université de Montréal, Montréal, QC, Canada; CHU Sainte-Justine Research Center, Montreal, QC, Canada.
Daniel C KoboldtThe Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Odent SylvieService de Génétique clinique, CHU Rennes, ERN ITHACA, Rennes, France; University Rennes, CNRS, INSERM, IGDR (Institut de Génétique et développement de Rennes), UMR 6290, ERL U1305, Rennes, France.
Marjolaine WillemsMedical Genetic Department for Rare Diseases and Personalized Medicine, Reference Center AD SOOR, AnDDI-RARE, Inserm U1298, INM, Montpellier University, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
Wen-Hann TanDivision of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Benjamin CogneNantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France; Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.
Claudine RieublandDepartment of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Dominique BraunDepartment of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Scott Douglas McLeanDivision of Clinical Genetics, The Children's Hospital of San Antonio, San Antonio, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Konrad PlatzerInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Pia ZacherEpilepsy Center Kleinwachau, Dresden-Radeberg, Germany.
Henry OppermannInstitute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
Lucie EvenepoelCentre de Génétique Humaine, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Avenue Hippocrate 10-1200, Brussels, Belgium.
Pierre BlancSorbonne Université, Department of Medical Genetics, APHP, Pitié-Salpêtrière hospital, Paris Brain Institute-ICM, Laboratoire SeqOIA-PFMG2025, Paris, France.
Laïla El KhattabiDepartment of Medical Genetics, APHP, Armand Trousseau and Pitié-Salpêtrière hospitals, Brain Development team, Paris Brain Institute-ICM, Sorbonne Université, Paris, France; Laboratoire SeqOIA-PFMG2025, Paris, France.
Neshatul HaqueBioinformatics Research and Development Laboratory, Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Nikita R DsouzaBioinformatics Research and Development Laboratory, Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Michael T ZimmermannBioinformatics Research and Development Laboratory, Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA; Clinical and Translational Sciences Institute, Medical College of Wisconsin, Milwaukee, WI, USA.
Raul UrrutiaDepartment of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
Eric W KleeDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN, USA; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Yiping ShenDivision of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; SynerGene Education, Hejun College, Huichang Jiangxi, China.
Hongzhen DuState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
Leonard RappaportDivision of Developmental Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Chang-Mei LiuState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China. Electronic address: liuchm@ioz.ac.cn.
Xiaoli ChenDepartment of Medical Genetics, Capital Institute of Pediatrics, Beijing, China; Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: xiaolichen@pumc.edu.cn.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microtubule affinity-regulating kinase 2 (MARK2) contributes to establishing neuronal polarity and developing dendritic spines. Although large-scale sequencing studies have associated MARK2 variants with autism spectrum disorder (ASD), the clinical features and variant spectrum in affected individuals with MARK2 variants, early developmental phenotypes in mutant human neurons, and the pathogenic mechanism underlying effects on neuronal development have remained unclear. Here, we report 31 individuals with MARK2 variants and presenting with ASD, other neurodevelopmental disorders, and distinctive facial features. Loss-of-function (LoF) variants predominate (81%) in affected individuals, while computational analysis and in vitro expression assay of missense variants supported the effect of MARK2 loss. Using proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs), we show that MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and dis-organization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2
Indexed as
Autism Spectrum DisorderInduced Pluripotent Stem CellsProtein Serine-Threonine KinasesWnt Signaling PathwayAdolescentAnimalsbeta CateninCell DifferentiationChildChild, PreschoolDown-RegulationFemaleHumansMaleMiceNeural Stem Cellsbeta CateninProtein Serine-Threonine KinasesASDautism spectrum disorderlithiumLoFloss-of-functionMARK2 variantsWNT/β-catenin signaling pathway
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