Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome
A triplet repeat expansion leading to transcriptional silencing of the <i>FMR1</i> 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 trial...
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MDPI AG
2020-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/2/289 |
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| author | Noora Putkonen Asta Laiho Doug Ethell Juha Pursiheimo Anna-Kaisa Anttonen Juho Pitkonen Adriana M. Gentile Yolanda de Diego-Otero Maija L. Castrén |
| author_facet | Noora Putkonen Asta Laiho Doug Ethell Juha Pursiheimo Anna-Kaisa Anttonen Juho Pitkonen Adriana M. Gentile Yolanda de Diego-Otero Maija L. Castrén |
| author_sort | Noora Putkonen |
| collection | DOAJ |
| description | A triplet repeat expansion leading to transcriptional silencing of the <i>FMR1</i> 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. |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:20:30Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-1c9531baa28f4443aa9700608cccba122023-09-03T02:15:22ZengMDPI AGCells2073-44092020-01-019228910.3390/cells9020289cells9020289Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X SyndromeNoora Putkonen0Asta Laiho1Doug Ethell2Juha Pursiheimo3Anna-Kaisa Anttonen4Juho Pitkonen5Adriana M. Gentile6Yolanda de Diego-Otero7Maija L. Castrén8Faculty of Medicine, Physiology, University of Helsinki, FI-00014 Helsinki, FinlandTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistökatu 6A, FI-20520 Turku, FinlandLeucadia Therapeutics Inc., Riverside, CA 92506, USAThe Joint Clinical Biochemistry Laboratory of University of Turku, University Central Hospital and Wallac Oy, FI-20520 Turku, FinlandDepartment of Clinical Genetics, University Hospital of Helsinki, 160, FI-00290 Helsinki, FinlandFaculty of Medicine, Physiology, University of Helsinki, FI-00014 Helsinki, FinlandInstitute of Biomedical Research of Malaga (IBIMA) and Mental Health Unit, Regional University Hospital of Malaga, University of Malaga, Research lab. Hospital Civil, Pab-6 sot. 29009 Malaga, SpainInstitute of Biomedical Research of Malaga (IBIMA) and Mental Health Unit, Regional University Hospital of Malaga, University of Malaga, Research lab. Hospital Civil, Pab-6 sot. 29009 Malaga, SpainFaculty of Medicine, Physiology, University of Helsinki, FI-00014 Helsinki, FinlandA triplet repeat expansion leading to transcriptional silencing of the <i>FMR1</i> 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.https://www.mdpi.com/2073-4409/9/2/289disease biomarkerurine mirnafragile x syndromeautismmir-125a |
| spellingShingle | Noora Putkonen Asta Laiho Doug Ethell Juha Pursiheimo Anna-Kaisa Anttonen Juho Pitkonen Adriana M. Gentile Yolanda de Diego-Otero Maija L. Castrén Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome Cells disease biomarker urine mirna fragile x syndrome autism mir-125a |
| title | Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome |
| title_full | Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome |
| title_fullStr | Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome |
| title_full_unstemmed | Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome |
| title_short | Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome |
| title_sort | urine microrna profiling displays mir 125a dysregulation in children with fragile x syndrome |
| topic | disease biomarker urine mirna fragile x syndrome autism mir-125a |
| url | https://www.mdpi.com/2073-4409/9/2/289 |
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