T14484C and T14502C in the mitochondrial ND6 gene are associated with Leber’s hereditary optic neuropathy in a Chinese family

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited ocular disease which has been associated with three primary mitochondrial DNA mutations: G3640A, G11778A, and T14484C. In this study, we clinically characterized a Chinese family with complete penetrance of LHON. The patients in the family presented with variable clinical features. By direct DNA sequence analysis, we identified both T14484C mutation and a nearby T to C variant at nucleotide 14502 of mitochondria DNA. The T14502C variant altered I58 to V of the protein ND6, which was present in all patients of the family, but not in four unaffected family members and 200 normal controls. The co-existence of both T14484C mutation and T14502C substitution in all patients from the same LHON family suggests that T14502C may play a synergistic role with the primary mutation T14484C. The two variants together may account for the complete penetrance and absence of marked gender bias and visual recovery in the Chinese LHON family although we cannot exclude the possibility of simultaneous involvement of additional mitochondrial variant(s).