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

Br J Ophthalmol. 2017 Sep;101(9):1298-1302. doi: 10.1136/bjophthalmol-2017-310370. Epub 2017 Jul 20.

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.

Keywords: MTTKgene; Mitochondrial DNA; mitochondrial DNA mutations; mitochondrial eye disease.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / metabolism
  • Electrooculography
  • Electroretinography
  • Humans
  • Male
  • Mitochondria, Muscle / enzymology
  • Mitochondria, Muscle / genetics
  • Mitochondria, Muscle / pathology
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Optical Imaging
  • Photoreceptor Cells, Vertebrate / pathology*
  • Point Mutation*
  • RNA, Transfer, Lys / genetics*
  • Succinate Dehydrogenase / metabolism
  • Thymidine Kinase / genetics*
  • Usher Syndromes / diagnosis
  • Usher Syndromes / enzymology
  • Usher Syndromes / genetics*

Substances

  • DNA, Mitochondrial
  • RNA, Transfer, Lys
  • Succinate Dehydrogenase
  • Electron Transport Complex IV
  • thymidine kinase 2
  • Thymidine Kinase