“Myo-neuropathy” is commonly associated with mitochondrial tRNALysine mutation

Abstract

The mitochondrial tRNALys (mt-tRNALys) mutation is initially associated with myoclonic epilepsy and ragged-red fibers (MERRF). The clinical, laboratory, morphologic and molecular findings from 22 mt-tRNALys mutation carriers from local database in East China were analyzed retrospectively. We identified 13 symptomatic and 9 asymptomatic individuals with a known pathogenic mitochondrial tRNALys mutation. The most common mutations were m.8344 A>G (81.8%), m.8363G>A (9.1%), m.8356 T>C (4.5%) and m.8356 T>G (4.5%). The degree of mutation heteroplasmy in blood was high both in symptomatic (mean 64.5%, range 41–82%) and asymptomatic individuals (mean 53.1%, range 21–78%). Age at onset ranged from 6 year-old to the age of 66 years (mean 35.8 ± 16.4 years old). The most frequent symptoms were muscle weakness (76.9%), exercise intolerance (76.9%), elevated creatine kinase levels (61.5%), peripheral neuropathy (69.2%) and cerebellar ataxia (61.5%), while myoclonus was only present in 23.1% of symptomatic patients. A diagnosis of mitochondrial myopathy (MM) and neuropathy ataxia and retinitis pigmentosa (NARP/NARP-like) syndrome was made in 77% of symptomatic patients, whereas the classic syndrome of myoclonic epilepsy with ragged-red fibers (MERRF) was rare (23%). In this cohort of patients with mt-tRNALys mutation, more than one third of our patients did not develop signs and symptoms of central nervous system involvement even in later stages of the disease, indicating the necessity to investigate the mt-tRNALys gene in ‘pure’ mitochondrial ‘myo-neuropathy’.

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Acknowledgements

The authors would like to thank the patients and families. This study was supported by the National Natural Science Foundation of China (81701237 and 81671235), People’s benefit project of science and technology in Qingdao (16-6-2-1-nsh) and the Taishan Scholars Program of Shandong Province.

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Correspondence to Wei Li.

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The study was performed according to the Declaration of Helsinki and approved by the ethical committee of the Qilu Hospital of Shandong University.

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Ji, K., Zhao, B., Lin, Y. et al. “Myo-neuropathy” is commonly associated with mitochondrial tRNALysine mutation. J Neurol (2020). https://doi.org/10.1007/s00415-020-10017-z

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Keywords

  • Mitochondrial disease
  • Mitochondrial tRNAlysine
  • m.8344A>G
  • MERRF