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.
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We are grateful to the participating patients and collaborating colleagues for collecting patients’ data and providing these within the German network for mitochondrial disorders (mitoNET). The study was funded by the German Bundesministerium für Bildung und Forschung (BMBF) through the German Network for mitochondrial disorders (mitoNET; 01GM1113A to B. B. and T. K. for the registry, 01GM1113C to H. P. for biobanking and molecular diagnostics). K. G. Claeys received research Grants unrelated to the current study from the Deutsche Gesellschaft für Muskelkranke e.V. (DGM).
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflict of interest.
The study was performed according to the Declaration of Helsinki and approved by the ethical committee of the RWTH Aachen University and University Hospital München.
Written informed consent was obtained from the participants.
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