title: [Leber's hereditary optic neuropathy may be associated with the mitochondrial tRNAGlu A14693G mutation in three Chinese families].
abstract: We reported here the clinical, genetic and molecular characterization of three Han Chinese families with Leber's hereditary optic neuropathy. Ophthalmologic examinations revealed the variable severity and age-at-onset of visual loss among probands and other matrilineal relatives of these families. Strikingly, these families exhibited extremely low penetrances of visual impairment. Sequence analysis of complete mitochondrial genomes in these pedigrees identified the known homoplasmic tRNAGlu A14693G mutation and distinct sets of polymorphism belonging to haplogroups Y1b, Y1 and Y1, respectively. The A14693G mutation occurs at the extremely conserved nucleotide (conventional position 54) of tRNAGlu. Thus, this mutation may alter structural formation and stabilization of functional tRNAs, thereby leading to a failure in tRNA metabolism and mitochondrial dysfunction involved in visual impairment. However, none of other variants showed the evolutionary conservation and functional significance. These observations suggested that the tRNAGlu A14693G mutation may be involved in the pathogenesis of optic neuropathy in these families.
authors.affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China zhangyongmei0529@163.com
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhang
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Ji
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Liu
authors.forename: Xiang-Tian
authors.initials: XT
authors.lastname: Zhou
authors.forename: Fu-Xin
authors.initials: FX
authors.lastname: Zhao
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Sun
authors.forename: Qi-Ping
authors.initials: QP
authors.lastname: Wei
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
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; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D023281:Genomics; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D012343:RNA, Transfer / Q000235:genetics*
chemical_list: D012343:RNA, Transfer