Phenotypic diversity associated with the MT-TV gene m.1644G > A mutation, a matter of quantity

We describe four patients from three independent families with the m.1 644G> A in the MT-1Vgene, previously reported without demonstration of its deleterious impact. Very high mutation proportion co-segregated with cytochrome oxidase defect in single muscle fibers and respiratory defect in cybrids as shown by spectrophotometric assays and polarography. The mutation appeared to have a very steep threshold effect with asymptomatic life up to 70% mutation propor: tion, progressive encephalopathy above 80% and severe Leigh-like syndrome above 95% mutation. One patient did not fit within that frame but presented with characteristics suggesting the presence of an additional disease. (C) 2014 Elsevier B.V. and Mitochondria Research Society. All rights reserved.