Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome
Copyright policy )Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome
A triplet repeat expansion leading to transcriptional silencing of the FMR1 gene results in fragile X syndrome (FXS), which is a common cause of inherited intellectual disability and autism. Phenotypic variation requires personalized treatment approaches and hampers clinical trials in FXS. We searched for microRNA (miRNA) biomarkers for FXS using deep sequencing of urine and identified 28 differentially regulated miRNAs when 219 reliably identified miRNAs were compared in dizygotic twin boys who shared the same environment, but one had an FXS full mutation, and the other carried a premutation allele. The largest increase was found in miR-125a in the FXS sample, and the miR-125a levels were increased in two independent sets of urine samples from a total of 19 FXS children. Urine miR-125a levels appeared to increase with age in control subjects, but varied widely in FXS subjects. Should the results be generalized, it could suggest that two FXS subgroups existed. Predicted gene targets of the differentially regulated miRNAs are involved in molecular pathways that regulate developmental processes, homeostasis, and neuronal function. Regulation of miR-125a has been associated with type I metabotropic glutamate receptor signaling (mGluR), which has been explored as a treatment target for FXS, reinforcing the possibility that urine miR-125a may provide a novel biomarker for FXS.
- University of California System United States
- University of Helsinki
- University of Turku Finland
- Åbo Akademi University Finland
- Faculty of Medicine Indonesia
MECHANISM, Male, Síndrome del cromosoma X frágil, Autism, Intellectual disability, Urine, Receptors, Metabotropic Glutamate, MIRNA, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans, mir-125a, MiR-125a, Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs, fragile X syndrome, Child, MicroARNs, urine miRNA, High-Throughput Nucleotide Sequencing, MicroRNA, Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing, Discapacidad intelectual, Medical Subject Headings::Check Tags::Male, Genetics, developmental biology, physiology, Niño, Child, Preschool, Medical Subject Headings::Persons::Persons::Age Groups::Adolescent, Female, Medical Subject Headings::Persons::Persons::Age Groups::Child, Signal Transduction, EXPRESSION, Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability::Mental Retardation, X-Linked::Fragile X Syndrome, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation, Adolescent, fragile x syndrome, urine mirna, autism, disease biomarker, Article, RNAS, CIRCULATING MICRORNAS, miR-125a, Humans, Biochemistry, cell and molecular biology, Medical Subject Headings::Persons::Persons::Age Groups::Child::Child, Preschool, QH573-671, Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal Transduction, ta1182, Disease biomarker, Medical Subject Headings::Check Tags::Female, Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Metabotropic Glutamate, Orina, GENE, Urine miRNA, Biomedicine, MicroRNAs, Fragile X Syndrome, Mutation, Cytology, GENOMICS, Biomarkers, Fragile X syndrome
MECHANISM, Male, Síndrome del cromosoma X frágil, Autism, Intellectual disability, Urine, Receptors, Metabotropic Glutamate, MIRNA, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans, mir-125a, MiR-125a, Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs, fragile X syndrome, Child, MicroARNs, urine miRNA, High-Throughput Nucleotide Sequencing, MicroRNA, Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing, Discapacidad intelectual, Medical Subject Headings::Check Tags::Male, Genetics, developmental biology, physiology, Niño, Child, Preschool, Medical Subject Headings::Persons::Persons::Age Groups::Adolescent, Female, Medical Subject Headings::Persons::Persons::Age Groups::Child, Signal Transduction, EXPRESSION, Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability::Mental Retardation, X-Linked::Fragile X Syndrome, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation, Adolescent, fragile x syndrome, urine mirna, autism, disease biomarker, Article, RNAS, CIRCULATING MICRORNAS, miR-125a, Humans, Biochemistry, cell and molecular biology, Medical Subject Headings::Persons::Persons::Age Groups::Child::Child, Preschool, QH573-671, Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal Transduction, ta1182, Disease biomarker, Medical Subject Headings::Check Tags::Female, Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Metabotropic Glutamate, Orina, GENE, Urine miRNA, Biomedicine, MicroRNAs, Fragile X Syndrome, Mutation, Cytology, GENOMICS, Biomarkers, Fragile X syndrome
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