Article Text
Abstract
Background/Aim The rare mitochondrial DNA (mtDNA) variant m.8340G>A has been previously reported in the literature in a single, sporadic case of mitochondrial myopathy. In this report, we aim to investigate the case of a 39-year-old male patient with sensorineural deafness who presented to the eye clinic with nyctalopia, retinal pigmentary changes and bilateral cortical cataracts.
Methods The patient was examined clinically and investigated with autofluorescence, full-field electroretinography, electro-oculogram and dark adaptometry. Sequencing of the mitochondrial genome in blood and muscle tissue was followed by histochemical and biochemical analyses together with single fibre studies of a muscle biopsy to confirm a mitochondrial aetiology.
Results Electrophysiology, colour testing and dark adaptometry showed significant photoreceptor dysfunction with macular involvement. Sequencing the complete mitochondrial genome revealed a rare mitochondrial tRNALys (MTTK) gene variant—m.8340G>A—which was heteroplasmic in blood (11%) and skeletal muscle (65%) and cosegregated with cytochrome c oxidase-deficient fibres in single-fibre studies.
Conclusion We confirm the pathogenicity of the rare mitochondrial m.8340G>A variant the basis of single-fibre segregation studies and its association with an expanded clinical phenotype. Our case expands the phenotypic spectrum of diseases associated with mitochondrial tRNA point mutations, highlighting the importance of considering a mitochondrial diagnosis in similar cases presenting to the eye clinic and the importance of further genetic testing if standard mutational analysis does not yield a result.
- Mitochondrial DNA
- mitochondrial DNA mutations
- MTTKgene
- mitochondrial eye disease
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Footnotes
Contributors JSG: Concept, interpretation of data and preparation of manuscript. SAH: Experimental work and critical review of manuscript. ELB: Experimental work and critical review of manuscript. SH: Experimental work and critical review of manuscript. AHN: Concept, supervision, interpretation of data and critical review. CF: Experimental work. JP: Concept, supervision, interpretation of the data and critical review of the manuscript. RWT: Concept, supervision, interpretation of the data and critical review of the manuscript. SMD: Concept, supervision, interpretation of the data and critical review of the manuscript.
Funding This research received no specific grant from anyfunding agency in the public, commercial or not-for-profit sectors.
Competing interests RWT is supported by a Wellcome Trust Strategic Award (096919/Z/11/Z), the MRC Centre for Neuromuscular Diseases (G0601943), the Lily Foundation and the UK NHS Highly Specialised “Rare Mitochondrial Disorders of Adults and Children” Service in Newcastle upon Tyne.
Patient consent Patient.
Provenance and peer review Not commissioned; externally peer reviewed.