Using urine to diagnose large-scale mtDNA deletions in adult patients

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Varhaug , K N , Nido , G S , de Coo , I , Isohanni , P , Suomalainen , A , Tzoulis , C , Knappskog , P & Bindoff , L A 2020 , ' Using urine to diagnose large-scale mtDNA deletions in adult patients ' , Annals of Clinical and Translational Neurology , vol. 7 , no. 8 , pp. 1318-1326 .

Title: Using urine to diagnose large-scale mtDNA deletions in adult patients
Author: Varhaug, Kristin N.; Nido, Gonzalo S.; de Coo, Irenaeus; Isohanni, Pirjo; Suomalainen, Anu; Tzoulis, Charalampos; Knappskog, Per; Bindoff, Laurence A.
Contributor organization: HUS Children and Adolescents
Research Programs Unit
Anu Wartiovaara / Principal Investigator
Children's Hospital
STEMM - Stem Cells and Metabolism Research Program
Faculty of Medicine
University of Helsinki
Helsinki University Hospital Area
Department of Neurosciences
Neuroscience Center
Helsinki Institute of Life Science HiLIFE
Date: 2020-08
Language: eng
Number of pages: 9
Belongs to series: Annals of Clinical and Translational Neurology
ISSN: 2328-9503
Abstract: Objective: The aim of this study was to evaluate if urinary sediment cells offered a robust alternative to muscle biopsy for the diagnosis of single mtDNA deletions. Methods: Eleven adult patients with progressive external ophthalmoplegia and a known single mtDNA deletion were investigated. Urinary sediment cells were used to isolate DNA, which was then subjected to long-range polymerase chain reaction. Where available, the patient's muscle DNA was studied in parallel. Breakpoint and thus deletion size were identified using both Sanger sequencing and next generation sequencing. The level of heteroplasmy was determined using quantitative polymerase chain reaction. Results: We identified the deletion in urine in 9 of 11 cases giving a sensitivity of 80%. Breakpoints and deletion size were readily detectable in DNA extracted from urine. Mean heteroplasmy level in urine was 38% +/- 26 (range 8 - 84%), and 57% +/- 28 (range 12 - 94%) in muscle. While the heteroplasmy level in urinary sediment cells differed from that in muscle, we did find a statistically significant correlation between these two levels (R = 0.714, P = 0.031(Pearson correlation)). Interpretation: Our findings suggest that urine can be used to screen patients suspected clinically of having a single mtDNA deletion. Based on our data, the use of urine could considerably reduce the need for muscle biopsy in this patient group.
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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