Chronic progressive external ophthalmoplegia: a new heteroplasmic tRNA(Leu(CUN)) mutation of mitochondrial DNA.
We sequenced all genes of mitochondrial tRNAs of a patient with chronic progressive external ophthalmoplegia with 5% ragged red fibres and 15% COX-negative fibres but without macrorearrangements of mitochondrial DNA (mtDNA). Direct sequencing showed a novel heteroplasmic G>A substitution in position 12316 of tRNA(Leu(CUN)) gene. This change destroys a highly conserved G-C base coupling in tRNA TpsiC branch. By RFLP analysis we could demonstrate different degrees of heteroplasmy in different patient's tissues. This alteration, absent in a population of 110 patients with different encephalomyopathies, can be considered pathogenic: it is the tenth tRNA(Leu(CUN)) pathogenic mutation described up to date.
Cardaioli
E
E
Department of Neurological and Behavioural Sciences, University of Siena, Viale Bracci 2, Siena, Italy.
Da Pozzo
P
P
Malfatti
E
E
Gallus
G N
GN
Rubegni
A
A
Malandrini
A
A
Gaudiano
C
C
Guidi
L
L
Serni
G
G
Berti
G
G
Dotti
M T
MT
Federico
A
A
D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics* / Q000473:pathology; D012356:RNA, Transfer, Leu / Q000235:genetics*
D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu