Article Text

Serum microRNA as indicators of Wolfram syndrome’s progression in neuroimaging studies
  1. Agnieszka Zmyslowska1,
  2. Marcin Stanczak2,
  3. Zuzanna Nowicka2,
  4. Arleta Waszczykowska3,
  5. Dobromila Baranska4,
  6. Wojciech Fendler2,5,
  7. Maciej Borowiec1,
  8. Wojciech Młynarski6
  1. 1Department of Clinical Genetics, Medical University of Lodz, Lodz, Poland
  2. 2Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland
  3. 3Department of Ophthalmology and Vision Rehabilitation, Medical University of Lodz, Lodz, Poland
  4. 4Department of Diagnostic Imaging, Polish Mother’s Memorial Hospital Research Institute, Lodz, Poland
  5. 5Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
  6. 6Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland
  1. Correspondence to Dr Agnieszka Zmyslowska; agnieszka.zmyslowska{at}


Introduction Patients with the ultra-rare Wolfram syndrome (WFS) develop insulin-dependent diabetes and progressive neurodegeneration. The aim of the study was to quantify microRNAs (miRNAs) in sera from patients with WFS, correlate their expression with neurological imaging over time and compare miRNA levels with those observed in patients with type 1 diabetes mellitus (T1DM).

Research design and methods We quantified miRNA expression (Qiagen, Germany) in two groups of patients: with WFS at study entry (n=14) and after 2 years of follow-up and in 15 glycated hemoglobin-matched (p=0.72) patients with T1DM.

Results We observed dynamic changes in the expression of multiple miRNAs in patients with WFS parallel to disease progression and in comparison to the T1DM patients group. Among miRNAs that differed between baseline and follow-up WFS samples, the level of 5 increased over time (miR-375, miR-30d-5p, miR-30e-30, miR-145-5p and miR-193a-5p) and was inversely correlated with macular average thickness, while the expression of 2 (let-7g-5p and miR-22-3p) decreased and was directly correlated with neuroimaging indicators of neurodegeneration.

Conclusions Our findings show for the first time that serum miRNAs can be used as easily accessible indicators of disease progression in patients with WFS, potentially facilitating clinical trials on mitigating neurodegeneration.

  • diabetes mellitus
  • type 1
  • biomarkers
  • genetic diseases
  • inborn

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • MB and WM contributed equally.

  • Contributors AZ collected clinical data and wrote the draft of the manuscript. MS and ZN performed statistical analyses. AW performed and analyzed ophthalmological studies. DB performed and analyzed MRI studies. WF performed statistical analyses and contributed to writing the manuscript. MB performed genetic analyses. WM designed the study and collected the clinical data.

  • Funding This study was supported by National Science Centre grants no 2014/15/B/NZ5/01579, 2013/09/B/NZ5/00779 and by the Polish Ministry of Science and Higher Education No 2328/EURO-WABB/11/2012/2.

  • Disclaimer AZ and WF are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol was approved by the University Bioethics Committee at the Medical University in Lodz, Poland (RNN/73/14/KE).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.