A sporadic case of a heteroplasmic substitution in position 12316G>A in MT-TL2 causing cPEO with COX-negative fibers and RRF was described [99]; Karadimas CL et al. described an m.12315G>A mutation in the MT-TL2 gene in a woman with cPEO [100]; Soldath P et al. reported an m.12294 G>A in the MT-TL2 gene in an individual with cPEO and exercise intolerance [101]. The gene discussed is COX5A; the disease is External ophthalmoplegia.