Intra‐patient variability of heteroplasmy levels in urinary epithelial cells in carriers of the m.3243A>G mutation. Issue 2 (4th December 2018)

• Record Type: Journal Article
• Authors: de Laat, Paul; Rodenburg, Richard J.; Smeitink, Jan A. M.; Janssen, Mirian C. H.
• Is Part Of: Molecular genetics & genomic medicine. Volume 7:Issue 2(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-12-04
• Subjects: heteroplasmy -- m.3243A>G -- maternally inherited diabetes deafness -- mitochondrial medicine -- mitochondrial myopathy -- encephalopathy -- lactic acidosis and stroke‐like episodes -- NMDAS -- outcome measures; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.523
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: The mitochondrial DNA m.3243A>G mutation is one the most prevalent mutation causing mitochondrial disease in adult patients. Several cohort studies have used heteroplasmy levels in urinary epithelial cells (UEC) to correlate the genotype of the patients to the clinical severity. However, the interpretation of these data is hampered by a lack of knowledge on the intra‐patient variability of the heteroplasmy levels. The goal of this study was to determine the day‐to‐day variation of the heteroplasmy levels in UEC. Methods: Fifteen carriers of the m.3243A>G mutation collected five urine samples in a 14‐day window. Heteroplasmy levels of the m.3243A>G mutation were determined in these samples. Data from the national cohort study, including Newcastle Mitochondrial Disease Adult Scale scores and clinical diagnosis, were used. Results: In the samples of six patients, heteroplasmy levels were within a 5% margin. In the samples collected from five patients, the margin was >20%. Conclusion: Heteroplasmy levels of UEC in carriers of the m.3243A>G mutation have a significant day‐to‐day variation. The interpretation of a correlation between heteroplasmy levels in urine and disease severity is therefore not reliable. Therefore, heteroplasmy levels in UEC should not be used as a prognostic biomarker in these patients. Abstract : In this study, we showed that the measurement of heteroplasmy in urinary epithelial cells has a substantial intra‐patient variability and is therefore unfit to be used as a prognostic biomarker in patients carrying the m.3243A>G mutation. This should be taken into account in the evaluation of relevant biomarkers for carriers of the m.3243A>G mutation.