During the past 16 years since the delineation of the human mitochondr
ial genome, substantial advances have been made in identifying pathoge
nic mutations causing mitochondrial disorders. However, just as we hav
e come to accept the unexpected in the nontraditional aspects of Mende
lian inheritance with the discovery of trinucleotide expansions, impri
nting and uniparental disomy, unusual characteristics of mitochondrial
inheritance also have been found that defy existing laws. For example
, we now know that the nuclear genetic background of an individual mig
ht influence the expression and tissue specificity of mitochondrial mu
tations. Pathogenic mitochondrial DNA mutations contribute to the gene
ration of new mutations by compromising mitochondrial function and inc
reasing free radical production. Evidence for recombination raises new
questions about repair mechanisms of mitochondrial DNA. It appears th
at the more we learn about the bases of mitochondrial disease, the mor
e complex diagnosis, treatment, and genetic counseling become. (C) Rap
id Science Publishers.