Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders
Copyright policy )Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders
AbstractPostsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2—whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.
- Vrije Universiteit Amsterdam Netherlands
- Washington State University United States
- University of Padua Italy
- Leiden University Medical Center Netherlands
- Radboud university medical center
Male, Developmental Disabilities, Muscle Proteins, [SDV.GEN] Life Sciences [q-bio]/Genetics, ANNOTATION, Whole Exome Sequencing, Craniofacial Abnormalities, Drosophila Proteins, Child, SYNAPTIC DEVELOPMENT, Neurons, Behavior, Animal, Radboudumc 12: Sensory disorders DCMN: Donders Center for Medical Neuroscience, Mental Disorders, Q, Brain, Drosophila melanogaster, Child, Preschool, Female, Neuroglia, Adult, GENES, Adolescent, Science, 610, Radboud University Medical Center, Nerve Tissue Proteins, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Article, Young Adult, RESOURCE, Intellectual Disability, 616, Exome Sequencing, Animals, Humans, Language Development Disorders, Autistic Disorder, Preschool, [SDV.GEN]Life Sciences [q-bio]/Genetics, Behavior, Epilepsy, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience, Animal, MEMORY, Proteins, Membrane Proteins, Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health Sciences, FRAMEWORK, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurodevelopmental Disorders, DE-NOVO MUTATIONS, Mutation, Human Genetics - Radboud University Medical Center
Male, Developmental Disabilities, Muscle Proteins, [SDV.GEN] Life Sciences [q-bio]/Genetics, ANNOTATION, Whole Exome Sequencing, Craniofacial Abnormalities, Drosophila Proteins, Child, SYNAPTIC DEVELOPMENT, Neurons, Behavior, Animal, Radboudumc 12: Sensory disorders DCMN: Donders Center for Medical Neuroscience, Mental Disorders, Q, Brain, Drosophila melanogaster, Child, Preschool, Female, Neuroglia, Adult, GENES, Adolescent, Science, 610, Radboud University Medical Center, Nerve Tissue Proteins, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Article, Young Adult, RESOURCE, Intellectual Disability, 616, Exome Sequencing, Animals, Humans, Language Development Disorders, Autistic Disorder, Preschool, [SDV.GEN]Life Sciences [q-bio]/Genetics, Behavior, Epilepsy, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience, Animal, MEMORY, Proteins, Membrane Proteins, Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health Sciences, FRAMEWORK, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurodevelopmental Disorders, DE-NOVO MUTATIONS, Mutation, Human Genetics - Radboud University Medical Center
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