title: Mutation in the mitochondrial tRNA(Ile) gene causes progressive myoclonus epilepsy.
abstract: OBJECTIVE
  The group of the rare progressive myoclonic epilepsies (PME) include a wide spectrum of mitochondrial and metabolic diseases. In juvenile and adult ages, MERRF (myoclonic epilepsy with ragged red fibres) is the most common form. The underlying genetic defect in most patients with the syndrome of MERRF is a mutation in the tRNALys gene, but mutations were also detected in the tRNAPhe gene.
  
  
  METHODS
  Here, we describe a 40 year old patient with prominent myoclonic seizures since 39 years of age without a mutation in the known genes who underwent intensive clinical, genetic and functional workup.
  
  
  RESULTS
  The patient had a slight mental retardation and a severe progressive hearing loss based on a defect of the inner ear on both sides. Ictal electroencephalography (EEG) showed bilateral occipital and generalized spikes and polyspikes induced and aggravated by photostimulation. A cranial magnetic resonance imaging (cMRI) detected a global cortical atrophy of the brain and mild periventricular white matter lesions. The electromyography (EMG) was normal but the muscle biopsy showed abundant ragged red fibres. Sequencing of the mitochondrial DNA from the skeletal muscle biopsy revealed a novel heteroplasmic mutation (m.4279A>G) in the tRNAIle gene which was functionally relevant as tested in single skeletal muscle fibre investigations.
  
  
  CONCLUSIONS
  Mutations in tRNAIle were described in patients with chronic progressive external ophthalmoplegia (CPEO), prominent deafness or cardiomyopathy but, up to now, not in patients with myoclonic epilepsy. The degree of heteroplasmy of this novel mitochondrial DNA mutation was 70% in skeletal muscle but only 15% in blood, pointing to the diagnostic importance of a skeletal muscle biopsy also in patients with myoclonic epilepsy.
authors.affiliation: Department of Epileptology and Life&Brain Center, University of Bonn, Germany. gabor.zsurka@ukb.uni-bonn.de
authors.forename: Gábor
authors.initials: G
authors.lastname: Zsurka
authors.forename: Felicitas
authors.initials: F
authors.lastname: Becker
authors.forename: Markus
authors.initials: M
authors.lastname: Heinen
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Gdynia
authors.forename: Holger
authors.initials: H
authors.lastname: Lerche
authors.forename: Wolfram S
authors.initials: WS
authors.lastname: Kunz
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Weber
mesh_terms: D000328:Adult; D004569:Electroencephalography; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008931:Mitochondria, Muscle / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics*; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics*; D012343:RNA, Transfer / Q000235:genetics*
chemical_list: D012343:RNA, Transfer