Clinical and molecular findings in four new patients harbouring the mtDNA 8993T'C mutation

The 8993T>G (L156R) transversion in the mtDNA ATPase 6 gene is a common cause of maternally inherited Leigh syndrome (MILS; McKusick 516060). In vitro studies showed that L156R severely impairs ATP production by altering the proton channel of complex V (DiMauro and Schon 2001). A less common MILS mutation in the same gene (8993T>C; L156P) exhibits a milder phenotype and a remitting^relapsing clinical course, and shows no defective ATP synthesis. Its effects on cellular ATP output are generally unclear. We describe four new 8993T>C patients. In one case, we tested the effects of the mutation on energy production and mitochondrial membrane potential ðDcmÞ