6533b860fe1ef96bd12c3a09

RESEARCH PRODUCT

A new mitochondrial point mutation in the transfer RNALys gene associated with progressive external ophthalmoplegia with impaired respiratory regulation

Bert Obermaier-kusserHarald Von PeinMatthias F. BauerMario MörlCornelia MillesMartina JacobsJoachim WolfArmin J. Grau

subject

MaleOphthalmoplegia Chronic Progressive ExternalRNA MitochondrialMitochondrial diseaseMolecular Sequence DataRespiratory chainBiologymedicine.disease_causeSecondary PreventionmedicineHumansPoint MutationGeneticsMutationBase SequenceTransition (genetics)Point mutationExternal ophthalmoplegiaMiddle Agedmedicine.diseaseHeteroplasmyNeurologyRespiratory failureRNARNA Transfer LysNeurology (clinical)Respiratory Insufficiency

description

Abstract We report a novel heteroplasmic point mutation G8299A in the gene for mitochondrial tRNA Lys in a patient with progressive external ophthalmoplegia complicated by recurrent respiratory insufficiency. Biochemical analysis of respiratory chain complexes in muscle homogenate showed a combined complex I and IV deficiency. The transition does not represent a known neutral polymorphism and affects a position in the tRNA acceptor stem which is conserved in primates, leading to a destabilization of this functionally important domain. In vitro analysis of an essential maturation step of the tRNA transcript indicates the probable pathogenicity of this mutation. We hypothesize that there is a causal relationship between the novel G8299A transition and progressive external ophthalmoplegia with recurrent respiratory failure due to a depressed respiratory drive.

yearjournalcountryeditionlanguage
2011-11-03Journal of the Neurological Sciences
https://doi.org/10.1016/j.jns.2012.01.013