Mutations in SURF1 were the first to be identified in association with any COX assembly factor [76]—and, in fact, in any nuclear gene encoding proteins associated with structure, function, or assembly of COX—in a series of patients with Leigh disease, otherwise known as subacute necrotizing encephalomyopathy [77], which is often accompanied by systemic COX deficiency. The gene discussed is SURF1; the disease is Leigh syndrome.