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Case Reports
. 2017 May 18;17(1):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

Laura Kytövuori  1   2   3 , Mikko Kärppä  4   5   6 , Hannu Tuominen  7 , Johanna Uusimaa  5   8   9   10 , Markku Saari  11 , Reetta Hinttala  5   8   9   10 , Kari Majamaa  4   5   6
Affiliations
Case Reports

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

Laura Kytövuori et al. BMC Neurol. .

Abstract

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.

Keywords: Case report; Cytochrome c oxidase deficiency; Mitochondrial diseases; Neuromuscular disorders.

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Figures

Fig. 1
Fig. 1
Histology of vastus lateralis muscle from the patient harboring the m.8156delG mutation. a Hematoxylin and eosin stainings show ragged red fibers. Bar = 50 μm (b) SDH-COX staining shows that COX-deficient fibers encompass more than half of the fibers. Bar = 50 μm (c) NADH staining shows mitochondrial proliferation. Bar = 100 μm
Fig. 2
Fig. 2
Novel frameshift mutation in MT-CO2 alters and truncates the C-terminus of COX2. a The deletion m.8156delG was found in the proband, but not in the asymptomatic mother or siblings, suggesting that the mutation had arisen de novo. b The deletion was found in three tissues of the proband. c The mutation alters the amino acid sequence of the C-terminus of COX2 beyond amino acid 190 and creates a stop codon at position 211
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