Expanded phenotypic spectrum of the m.8344AG 'MERRF' mutation: data from the German mitoNET registry
| Autor: | Aleksandra Nadaj-Pakleza, Kristl G. Claeys, Holger Prokisch, Jörg B. Schulz, Ronald R. Lautenschläger, Joachim Weis, Klaus A. Kuhn, Thomas Klopstock, Jochen Schäfer, Marcus Deschauer, Cornelia Kornblum, Judith Altmann, Robert Kopajtich, Sandra Jackson, Diana Lehmann, Ludger Schöls, Boriana Büchner, Kathrin N. Karle |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Pathology RNA Mitochondrial Cohort Studies Epilepsy 0302 clinical medicine epidemiology [MERRF Syndrome] Mitochondrial myopathy Germany Medicine genetics [RNA] Registries Age of Onset genetics [MERRF Syndrome] Brain Middle Aged Heteroplasmy Pedigree Phenotype Neurology RNA Transfer Lys Female medicine.symptom Adult medicine.medical_specialty Ataxia Adolescent Mitochondrial disease genetics [RNA Transfer Lys] epidemiology [Germany] 03 medical and health sciences Humans ddc:610 diagnostic imaging [Brain] Aged Cerebellar ataxia business.industry medicine.disease MERRF Syndrome 030104 developmental biology drug therapy [MERRF Syndrome] physiopathology [MERRF Syndrome] Mutation Myoclonic epilepsy RNA Neurology (clinical) business Myoclonus 030217 neurology & neurosurgery |
| Zdroj: | Journal of neurology 263(5), 961-972 (2016). doi:10.1007/s00415-016-8086-3 |
| ISSN: | 1432-1459 |
| DOI: | 10.1007/s00415-016-8086-3 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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