Expanded phenotypic spectrum of the m.8344A>G "MERRF" mutation: data from the German mitoNET registry

J Neurol. 2016 May;263(5):961-972. doi: 10.1007/s00415-016-8086-3. Epub 2016 Mar 19.


The m.8344A>G mutation in the MTTK gene, which encodes the mitochondrial transfer RNA for lysine, is traditionally associated with myoclonic epilepsy and ragged-red fibres (MERRF), a multisystemic mitochondrial disease that is characterised by myoclonus, seizures, cerebellar ataxia, and mitochondrial myopathy with ragged-red fibres. We studied the clinical and paraclinical phenotype of 34 patients with the m.8344A>G mutation, mainly derived from the nationwide mitoREGISTER, the multicentric registry of the German network for mitochondrial disorders (mitoNET). Mean age at symptom onset was 24.5 years ±10.9 (6-48 years) with adult onset in 75 % of the patients. In our cohort, the canonical features seizures, myoclonus, cerebellar ataxia and ragged-red fibres that are traditionally associated with MERRF, occurred in only 61, 59, 70, and 63 % of the patients, respectively. In contrast, other features such as hearing impairment were even more frequently present (72 %). Other common features in our cohort were migraine (52 %), psychiatric disorders (54 %), respiratory dysfunction (45 %), gastrointestinal symptoms (38 %), dysarthria (36 %), and dysphagia (35 %). Brain MRI revealed cerebral and/or cerebellar atrophy in 43 % of our patients. There was no correlation between the heteroplasmy level in blood and age at onset or clinical phenotype. Our findings further broaden the clinical spectrum of the m.8344A>G mutation, document the large clinical variability between carriers of the same mutation, even within families and indicate an overlap of the phenotype with other mitochondrial DNA-associated syndromes.

Keywords: Ataxia; Epilepsy; Hearing impairment; Myoclonus; Psychiatric; Ragged-red fibres.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Brain / diagnostic imaging
  • Cohort Studies
  • Female
  • Germany / epidemiology
  • Humans
  • MERRF Syndrome / drug therapy
  • MERRF Syndrome / epidemiology
  • MERRF Syndrome / genetics*
  • MERRF Syndrome / physiopathology*
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Phenotype
  • RNA / genetics*
  • RNA, Mitochondrial
  • RNA, Transfer, Lys / genetics*
  • Registries


  • RNA, Mitochondrial
  • RNA, Transfer, Lys
  • RNA