Pigmentary retinopathy, rod–cone dysfunction and sensorineural deafness associated with a rare mitochondrial tRNALys(m.8340G>A) gene variant

Background/AimThe 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.MethodsThe 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.ResultsElectrophysiology, 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 coxidase-deficient fibres in single-fibre studies.ConclusionWe 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.