Identification of microRNAs associated with human fragile X syndrome using next-generation sequencing
Maryam Sotoudeh Anvari1, Hamed Vasei2, Hossein Najmabadi3
1Department of Molecular Pathology, School of Medicine, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. Dr_msotudeh@yahoo.com.
Abstract:
Fragile X syndrome (FXS) is caused by a mutation in the FMR1 gene which can lead to a loss or shortage of the FMR1 protein. This protein interacts with specific miRNAs and can cause a range of neurological disorders. Therefore, miRNAs could act as a novel class of biomarkers for common CNS diseases. This study aimed to test this theory by exploring the expression profiles of various miRNAs in Iranian using deep sequencing-based technologies and validating the miRNAs affecting the expression of the FMR1 gene. Blood samples were taken from 15 patients with FXS (9 males, 6 females) and 12 controls. 25 miRNAs were differentially expressed in individuals with FXS compared to controls. Levels of 9 miRNAs were found to be significantly changed (3 upregulated and 6 downregulated). In Patients, the levels of hsa-miR-532-5p, hsa-miR-652-3p and hsa-miR-4797-3p were significantly upregulated while levels of hsa-miR-191-5p, hsa-miR-181-5p, hsa-miR-26a-5p, hsa-miR-30e-5p, hsa-miR-186-5p, and hsa-miR-4797-5p exhibited significant downregulation; and these dysregulations were confirmed by RT-qPCR. This study presents among the first evidence of altered miRNA expression in blood samples from patients with FXS, which could be used for diagnostic, prognostic, and treatment purposes. Larger studies are required to confirm these preliminary results.
Insights
Fragile X syndrome (FXS) is linked to FMR1 gene mutations. This study found altered microRNA (miRNA) expression in FXS patients, suggesting miRNAs as potential biomarkers for neurological disorders.
Area of Science:
- Neuroscience
- Genetics
- Biomarker Discovery
Background:
- Fragile X syndrome (FXS) results from FMR1 gene mutations, impacting FMR1 protein levels and potentially causing neurological disorders.
- MicroRNAs (miRNAs) are implicated in gene regulation and may serve as biomarkers for central nervous system (CNS) diseases.
Purpose of the Study:
- To investigate miRNA expression profiles in Iranian individuals with FXS.
- To identify specific miRNAs that are differentially expressed in FXS patients compared to controls.
- To validate miRNAs that influence FMR1 gene expression.
Main Methods:
- Deep sequencing technology was employed to analyze miRNA expression in blood samples.
- Blood samples were collected from 15 FXS patients (9 males, 6 females) and 12 healthy controls.
- Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used for miRNA validation.
Main Results:
- Twenty-five miRNAs showed differential expression in FXS patients versus controls.
- Nine miRNAs exhibited significant expression changes: three upregulated (hsa-miR-532-5p, hsa-miR-652-3p, hsa-miR-4797-3p) and six downregulated (hsa-miR-191-5p, hsa-miR-181-5p, hsa-miR-26a-5p, hsa-miR-30e-5p, hsa-miR-186-5p, hsa-miR-4797-5p).
- These dysregulations were confirmed by RT-qPCR.
Conclusions:
- This study provides initial evidence of altered miRNA expression in the blood of FXS patients.
- Identified miRNAs could serve as novel biomarkers for FXS diagnosis, prognosis, and treatment.
- Further research with larger cohorts is necessary to confirm these findings.
More Related Videos
11:10Dissecting Cell-Autonomous Function of Fragile X Mental Retardation Protein in an Auditory Circuit by In Ovo Electroporation
Published on: July 6, 2022
10:59Generation and Characterization of Human Induced Pluripotent Stem Cell-derived Astrocytes Lacking Fragile X Messenger Ribonucleoprotein
Published on: June 6, 2025