University of Oulu

Soini, Heidi K.; Väisänen, Antti; Kärppä, Mikko; Hinttala, Reetta; Kytövuori, Laura; Moilanen, Jukka S.; Uusimaa, Johanna; Majamaa, Kari. A novel MTTT mutation m.15933G > A revealed in analysis of mitochondrial DNA in patients with suspected mitochondrial disease. BMC Medical Genetics 201718:14. DOI: 10.1186/s12881-017-0377-8

A novel MTTT mutation m.15933G > A revealed in analysis of mitochondrial DNA in patients with suspected mitochondrial disease

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Author: Soini, Heidi K.1,2,3,4; Väisänen, Antti1,2,3; Kärppä, Mikko1,2,3;
Organizations: 1Research Unit of Clinical Neuroscience, Neurology, University of Oulu
2Medical Research Center Oulu, Oulu University Hospital and University of Oulu
3Department of Neurology, Oulu University Hospital
4PEDEGO Research Unit, Pediatrics, University of Oulu
5Department of Pediatrics, Oulu University Hospital
6Department of Clinical Genetics, Oulu University Hospital
7PEDEGO Research Unit, Clinical Genetics, University of Oulu
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.9 MB)
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Language: English
Published: Springer Nature, 2017
Publish Date: 2017-05-19


Background: Mitochondrial diseases present with variable multi-organ symptoms. Common disease-causing mutations in mitochondrial DNA (mtDNA) are regularly screened in diagnostic work-up, but novel mutations may remain unnoticed.

Methods: Patients (N = 66) with a clinical suspicion of mitochondrial disease were screened for their mtDNA coding region using conformation sensitive gel electrophoresis and sequencing. Long-PCR was used to detect deletions followed by POLG1 sequencing in patients with multiple deletions.

Results: We discovered three novel mtDNA variants that included m.8743G > C, m.11322A > G and m.15933G > A. The novel MTTT variant m.15933G > A is suggested to be pathogenic. Analysis revealed also multiple mtDNA deletions in two patients and five nonsynonymous variants that were putatively pathogenic according to in-silico prediction algorithms. In addition, a rare haplogroup H associated m.7585_7586insT variant was discovered.

Conclusion: Among patients with a suspected mitochondrial disease, a novel MTTT variant m.15933G > A was discovered and is suggested to be pathogenic. In addition, several putatively pathogenic nonsynonymous variants and rare variants were found. These findings highlight the importance of coding region mtDNA screening among patients with clinical features suggesting a mitochondrial disease, but who lack the common mitochondrial disease mutations.

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Series: BMC medical genetics
ISSN: 1471-2350
ISSN-E: 1471-2350
ISSN-L: 1471-2350
Volume: 18
Article number: 14
DOI: 10.1186/s12881-017-0377-8
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
1184 Genetics, developmental biology, physiology
3111 Biomedicine
Funding: This study was supported by grants from Academy of Finland (project numbers 107174, 127764 and 266498), the Sigrid Juselius Foundation, the Finnish Graduate School for Population Genetics, the Päivikki and Sakari Sohlberg Foundation, The Alma and K.A. Snellman Foundation and the University of Oulu, Finland.
Academy of Finland Grant Number: 127764
Detailed Information: 127764 (Academy of Finland Funding decision)
266498 (Academy of Finland Funding decision)
Dataset Reference: Patient mtDNA sequences are available in GenBank: KY496857-KY496890.
Copyright information: © The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.