title: Leber's hereditary optic neuropathy is associated with mitochondrial ND6 T14502C mutation.
abstract: We report here the clinical, genetic, and molecular characterization of three Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age of onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T14502C (I58V) mutation, which localized at a highly conserved isoleucine at position 58 of ND6, and distinct sets of mtDNA polymorphisms belonging to haplogroups M10a, F1a1, and H2. The occurrence of T14502C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Here, mtDNA variants I187T in the ND1, A122V in CO1, S99A in the A6, and V254I in CO3 exhibited an evolutionary conservation, indicating a potential modifying role in the development of visual impairment associated with T14502C mutation in those families. Furthermore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic manifestation of the LHON-associated T14502C mutation in these Chinese families.
authors.affiliation: School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Fuxin
authors.initials: F
authors.lastname: Zhao
authors.forename: Minqiang
authors.initials: M
authors.lastname: Guan
authors.forename: Xiangtian
authors.initials: X
authors.lastname: Zhou
authors.forename: Meixia
authors.initials: M
authors.lastname: Yuan
authors.forename: Ming
authors.initials: M
authors.lastname: Liang
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Tong
authors.forename: Qi-Ping
authors.initials: QP
authors.lastname: Wei
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Sun
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree
chemical_list: C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase