title: The novel G10680A mutation is associated with complete penetrance of the LHON/T14484C family.
abstract: We report the clinical and genetic characterization of a Chinese Leber's hereditary optic neuropathy (LHON) family with complete penetrance and high percentage of recovery. Sequence analysis of the complete mitochondrial DNA revealed the presence of heteroplasmic ND6/T14484C mutation and 27 other variants, belonging to the East-Asian haplogroup B4b'd. Of those variants, a novel homoplasmic G10680A mutation substituted a threonine for a highly conserved alanine at ND4L amino acid 71, which was not found in unaffected family members and 100 normal controls. It indicated that G10680A may play a synergistic role with the primary mutation T14484C, leading to the complete penetrance of LHON in the presenting family. In addition, the other modifier factors including nuclear background, mitochondrial haplotypes and other environmental factors should account for the phenotypic variability of visual impairment in this family.
authors.affiliation: Biomedical Engineering Center, Fujian Medical University, 88 Jiaotong Road, Fuzhou, Fujian 350004, China. Julian_yang@mail.fjmu.edu.cn
authors.forename: Juhua
authors.initials: J
authors.lastname: Yang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Tong
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Sanjie
authors.initials: S
authors.lastname: Chen
authors.forename: Zongfu
authors.initials: Z
authors.lastname: Cao
authors.forename: Chunmei
authors.initials: C
authors.lastname: Liu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xu
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001773:Blood Cells; D002681:China; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D019683:Penetrance; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; C098483:NADH dehydrogenase subunit 4; C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase