We then sequenced APOPT1 in five subjects characterized by cavitating leukoencephalopathy with posterior predominance, and found mutations in three individuals (S4, S5, and S6). Individuals S4 and S6 presented with severe COX deficiency whereas individual S5 was not investigated biochemically. Additional subjects with isolated cIV deficiency with or without unspecific leukoencephalopathic changes (n = 10) were also screened, but no further mutations were identified.