Correlation between the clinical symptoms and the proportion of mitochondrial DNA carrying the 8993 point mutation in the NARP syndrome.
We describe a four-generation family with a maternally inherited mitochondrial disorder. The symptoms were restricted to the CNS and muscle, the most common features being subacute necrotizing encephalomyopathy, cognitive impairment, ataxia, retinitis pigmentosa, infantile spasms, and optic atrophy. A point mutation at the nucleotide 8993 of the gene encoding subunit 6 of the ATP synthase, associated with the neurogenic muscle weakness, ataxia, retinitis pigmentosa (NARP) syndrome, was shown to be inherited maternally in this family, and a clear correlation was found between the clinical severity of the disease and the proportion of mutant mtDNA. Analysis of oxidative phosphorylation in mitochondria carrying 80% mutant mitochondrial DNA showed a reduction of the ATP generation rate coupled to substrate oxidation.
Mäkelä-Bengs
P
P
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Suomalainen
A
A
Majander
A
A
Rapola
J
J
Kalimo
H
H
Nuutila
A
A
Pihko
H
H
D000293:Adolescent; D000328:Adult; D002493:Central Nervous System Diseases / Q000201:enzymology / Q000235:genetics*; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000201:enzymology / Q000235:genetics*; D010085:Oxidative Phosphorylation; D010375:Pedigree; D017354:Point Mutation; D006180:Proton-Translocating ATPases / Q000235:genetics; D013577:Syndrome
D004272:DNA, Mitochondrial; D006180:Proton-Translocating ATPases