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Case Reports
. 2018 Sep 20;18(1):149.
doi: 10.1186/s12883-018-1159-4.

Mutation m.15923A>G in the MT-TT gene causes mild myopathy - case report of an adult-onset phenotype

Mikko Kärppä  1   2   3 , Laura Kytövuori  4   5   6 , Markku Saari  7 , Kari Majamaa  1   2   3
Affiliations
Case Reports

Mutation m.15923A>G in the MT-TT gene causes mild myopathy - case report of an adult-onset phenotype

Mikko Kärppä et al. BMC Neurol. .

Abstract

Background: Only five patients have previously been reported to harbor mutations in the MT-TT gene encoding mitochondrial tRNA threonine. The m.15923A > G mutation has been found in three severely affected children. One of these patients died within days after birth and two had a phenotype of myoclonic epilepsy with ragged red fibers (MERRF) in early childhood. We have now found the mutation in an adult patient with mild myopathy.

Case presentation: The patient is a 64-year-old Finnish man, who developed bilateral ptosis, diplopia and exercise intolerance in his fifties. Family history was unremarkable. Muscle histology showed cytochrome c-oxidase (COX) negative and ragged red fibres. The m.15923A > G mutation heteroplasmy was 33% in the skeletal muscle and 2% in buccal epithelial cells. The mutation was undetectable in the blood. Single-fibre analysis was performed and COX-negative fibres had a substantially higher heteroplasmy of 92%, than the normal fibres in which it was 43%.

Conclusions: We report the fourth patient with m. 15923A > G and with a remarkably milder phenotype than the previous three patients. Our findings and recent biochemical studies suggest that the mutation m.15923A > G is a definite disease-causing mutation. Our results also suggest that heteroplasmy of the m.15923A > G mutation correlates with the severity of the phenotype. This study expands the catalog of the phenotypes caused by mutations in mtDNA.

Keywords: Case report; Mitochondrial diseases; Mitochondrial tRNAThr; Neuromuscular disorders; Single-fibre analysis.

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Conflict of interest statement

Ethics approval and consent to participate

High standard of ethics according to the WMA Declaration of Helsinki was applied in all investigations and clinical work described in this manuscript. The study protocol was approved by the Oulu University Hospital ethics committee. Written informed consent of participation was obtained from the patient. A copy of the written consent is available for review by the Editor of this journal.

Consent for publication

Written informed consent to publish this case report was given by the patient.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Mutation m.15923A > G is situated in a conservative position and causes typical mitochondria myopathy. a Sequence chromatograms showing variable heteroplasmy. P, patient; COX+, biochemically normal fibers; COX−, cytochrome c-oxidase negative fibers. b Histology stainings. Left panel: Hematoxylin & eosin staining showing ragged red fibers. Right panel: Cytochrome c-oxidase staining showing COX-negative (blue) fibers. Arrows denote biochemically abnormal fibers. c Clustal Omega [15] alingnment for multiple sequences showing complete conservation between species
See this image and copyright information in PMC

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