A NEAR HOMOPLASMIC T8993G MTDNA MUTATION IN A PATIENT WITH ATYPIC LEIGH-SYNDROME NOT PRESENT IN THE MOTHERS TISSUES

We report an interesting case of a T8993G mutation in the muscle mtDNA of a 2-year-old girl who presented with myoclonia, developmental dela y, increased lactate concentration in CSF and cerebral MRI abnormaliti es without retinopathy, suggesting an atypical form of Leigh syndrome. Search for mutant molecules in the blood and skin fibroblasts of the patient's healthy mother as well as in the blood of the also unaffecte d patient's sister was unsuccessful. This 'sporadic' case of 8993 mtDN A mutation may be due either to a de novo mutation arising during ooge nesis (or early embryogenesis) or to a mutation pre-existing in oocyte s in a few mtDNA molecules and selected through a narrow bottleneck me chanism. Whatever the mechanism involved, this observation illustrates a complete shift of the mtDNA type in only one generation: from 0 to nearly 100% of mtDNA molecules with the T8993G mutation.