Progressive myoclonus epilepsy and mitochondrial myopathy associated with mutations in the tRNA(Ser(UCN)) gene.
We report seven unrelated families with mitochondrial tRNA(Ser(UCN)) gene mutations at three different loci. A novel G7497A mutation is found in two families, both of which present with progressive myopathy, ragged-red fibers, lactic acidosis, and deficiency of respiratory chain complexes I and IV. This mutation presumably affects the tertiary tRNA(Ser(UCN)) dihydrouridine interaction. Mutations 7472 insC and T7512C, found in three and two families, respectively, are associated with myoclonus epilepsy, deafness, ataxia, cognitive impairment, and complex IV deficiency. No ragged-red fibers or ultrastructural abnormalities are seen. It is interesting that 6 of our 7 index patients are apparently homoplasmic, indicating a minor pathogenetic power of the tRNA(Ser(UCN)) mutations.
Jaksch
M
M
Institute of Clinical Chemistry, Diagnostic Molecular Biology and Mitochondrial Genetics, Academic Hospital Schwabing, Munich, Germany.
Klopstock
T
T
Kurlemann
G
G
Dörner
M
M
Hofmann
S
S
Kleinle
S
S
Hegemann
S
S
Weissert
M
M
Müller-Höcker
J
J
Pongratz
D
D
Gerbitz
K D
KD
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004579:Electron Transport / Q000502:physiology; D004831:Epilepsies, Myoclonic / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009132:Muscles / Q000473:pathology; D009154:Mutation / Q000502:physiology*; D010375:Pedigree; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics
D012346:RNA, Transfer, Amino Acyl