A new mitochondrial point mutation in the transfer RNA(Lys) gene associated with progressive external ophthalmoplegia with impaired respiratory regulation.
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.
Department of Neurology, Klinikum Ludwigshafen, Germany. wolfj@klilu.de
Joachim
J
Wolf
Bert
B
Obermaier-Kusser
Martina
M
Jacobs
Cornelia
C
Milles
Mario
M
Mörl
Harald D
HD
von Pein
Armin J
AJ
Grau
Matthias F
MF
Bauer
D001483:Base Sequence; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017246:Ophthalmoplegia, Chronic Progressive External / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012357:RNA, Transfer, Lys / Q000235:genetics*; D012131:Respiratory Insufficiency / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D055502:Secondary Prevention
D000077278:RNA, Mitochondrial; D012357:RNA, Transfer, Lys; D012313:RNA