Sequence analysis of mitochondrial DNA in a new maternally inherited encephalomyopathy.
A heteroplasmic insertion of a 9-bp tandem repeat element was detected in the mitochondrial DNA of the maternal members of a large family. The mutation was contained within the non-coding region between the genes specifying subunit II of cytochrome c oxidase and tR-NA(Lys). The proband and most of his maternal relatives were affected by a late-onset mitochondrial encephalomyopathy of variable severity, characterized by a unique combination of symptoms. Extensive screening of a large series of DNA samples, collected from unrelated normal individuals as well as patients affected by different neurological disorders, consistently failed to detect the 9-bp insertion, with two exceptions: a patient suffering from a syndrome virtually identical to that described in our original family and a child affected by bilateral striatal necrosis, a disorder which has been attributed to impairment of mitochondrial oxidative phosphorylation. These considerations suggest that the 9-bp insertion is pathogenic and that the region affected by the mutation may play a previously unsuspected functional role in mtDNA gene expression.
Fabrizi
G M
GM
Institute of Neurological Science, University of Siena School of Medicine, Italy.
Tiranti
V
V
Mariotti
C
C
Guazzi
G C
GC
Malandrini
A
A
DiDonato
S
S
Zeviani
M
M
D000368:Aged; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D012091:Repetitive Sequences, Nucleic Acid; D014960:X Chromosome
D004272:DNA, Mitochondrial