Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions

Progressive external ophthalmoplegias (PEO) characterized by accumulation o f large-scale mitochondrial DNA (mtDNA) deletions are rare human diseases. We mapped a new locus for dominant PEO at 15q22-q26 in a Belgian pedigree a nd identified a heterozygous mutation (Y955C) in the polymerase motif B of the mtDNA polymerase gamma (POLG). We identified three additional POLG miss ense mutations compatible with recessive PEO In two nuclear families. POLG is the only DNA polymerase responsible for mtDNA replication.