ABSTRACT
Deficiencies in the activity of the components of the mitochondrial respiratory chain
can result from mutations in genes encoded in the mitochondrial (mtDNA) or nuclear
genomes. Mutations in mtDNA have been identified over the past decade in a wide spectrum
of clinical disorders, and attention has now turned to identifying nuclear gene defects.
Positional cloning, candidate gene analysis, and functional complementation in patient
cell lines have all been used with success. Mutations in gene coding for structural
subunits of the respiratory chain complexes appear to be less numerous than defects
in genes associated with some aspect of the biogenesis of the respiratory chain. Despite
the fact that many of the nuclear disease genes so far identified are ubiquitously
expressed, tissue specificity of the biochemical and clinical phenotype is the rule
rather than the exception. This selective vulnerability of different cell populations
remains unexplained. The majority of patients with a biochemical deficiency in one
or the other of the respiratory chain complexes do not yet have a molecular diagnosis.
KEYWORD
Mitochondrial disease - respiratory chain - Leigh syndrome - cardiomyopathy - encephalopathy
