University of Oulu

Kytövuori et al. BMC Neurology (2017) 17:96, DOI 10.1186/s12883-017-0883-5

Case report : a novel frameshift mutation in the mitochondrial cytochrome c oxidase II gene causing mitochondrial disorder

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Author: Kytövuori, Laura1,2,3; Kärppä, Mikko1,2,3; Tuominen, Hannu4;
Organizations: 1Research Unit of Clinical Neuroscience, University of Oulu
2Medical Research Center Oulu, Oulu University Hospital and University of Oulu
3Department of Neurology, Oulu University Hospital
4Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu and Department of Pathology, Oulu University Hospital
5PEDEGO Research Unit, University of Oulu
6Department of Children and Adolescents, Division of Pediatric Neurology, Oulu University Hospital
7Biocenter Oulu, University of Oulu
8Turku Centre for Biotechnology, Cell Imaging Core, University of Turku
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
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Language: English
Published: Springer Nature, 2017
Publish Date: 2017-07-05


Background: Mitochondrial cytochrome c oxidase 2, MT-CO2, encodes one of the three subunits, which form the catalytic core of cytochrome c oxidase (COX), complex IV. Mutations in MT-CO2 are rare and the associated phenotypes are variable including nonsyndromic and syndromic forms of mitochondrial diseases.

Case presentation: We describe a 30-year-old man with cognitive decline, epilepsy, psychosis, exercise intolerance, sensorineural hearing impairment, retinitis pigmentosa, cataract and lactic acidosis. COX-deficient fibers and ragged red fibers were abundant in the muscle. Sequencing of mitochondrial DNA (mtDNA) revealed a novel frameshift mutation m.8156delG that was predicted to cause altered C-terminal amino acid sequence and to lead to truncation of the COX subunit 2. The deletion was heteroplasmic being present in 26% of the mtDNA in blood, 33% in buccal mucosa and 95% in muscle. Deletion heteroplasmy correlated with COX-deficiency in muscle histochemistry. The mother and the siblings of the proband did not harbor the deletion.

Conclusions: The clinical features and muscle histology of the proband suggested a mitochondrial disorder. The m.8156delG deletion is a new addition to the short list of pathogenic mutations in the mtDNA-encoded subunits of COX. This case illustrates the importance of mtDNA sequence analysis in patients with an evident mitochondrial disorder.

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Series: BMC neurology
ISSN: 1471-2377
ISSN-E: 1471-2377
ISSN-L: 1471-2377
Volume: 17
Article number: 96
DOI: 10.1186/s12883-017-0883-5
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
3112 Neurosciences
Funding: The study was supported by grants from the Sigrid Juselius Foundation, Medical Research Center, University of Oulu and Oulu University Hospital, State research funding from Oulu University Hospital, and the Academy of Finland (R.H., decision numbers 266,498 and 273,790)
Academy of Finland Grant Number: 266498
Detailed Information: 266498 (Academy of Finland Funding decision)
273790 (Academy of Finland Funding decision)
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.