title: The mitochondrial tRNA(Glu) A14693G mutation may influence the phenotypic manifestation of ND1 G3460A mutation in a Chinese family with Leber's hereditary optic neuropathy.
abstract: We report here the clinical, genetic, and molecular characterization of one Han Chinese family with maternally transmitted Leber's hereditary optic neuropathy (LHON). Three of seven matrilineal relatives in this family exhibited the variable degree of central vision loss at the age of 12, 14, and 16 years old, respectively. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the ND1 G3460A mutation and 47 other variants, belonging to the Asian haplogroup M7b2. The G3460A mutation is present at homoplasmy in matrilineal relatives of this Chinese family. Of other variants, the homoplasmic A14693G mutation is of special interest as it was implicated to be associated with other mitochondrial disorders. This mutation is located at the TpsiC-loop, at conventional position 54 of tRNA(Glu). The uridine at this position (U54), which is highly conserved from bacteria to human mitochondria, has been implicated to be important for tRNA structure and function. Thus, the A14693G mutation may alter the tertiary structure of this tRNA, cause a failure in this tRNA metabolism, thereby worsening the mitochondrial dysfunction associated with the primary G3460A mutation. Therefore, the tRNA(Glu) A14693G mutation may have a potential modifier role in the phenotypic manifestation of the primary LHON-associated G3460A mutation in this Chinese family.
authors: School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China.
authors: Yi
authors: Y
authors: Tong
authors: Yijian
authors: Y
authors: Mao
authors: Xiangtian
authors: X
authors: Zhou
authors: Li
authors: L
authors: Yang
authors: Juanjuan
authors: J
authors: Zhang
authors: Wanshi
authors: W
authors: Cai
authors: Fuxing
authors: F
authors: Zhao
authors: Xinjian
authors: X
authors: Wang
authors: Fan
authors: F
authors: Lu
authors: Jia
authors: J
authors: Qu
authors: Min-Xin
authors: MX
authors: Guan
mesh_terms: D000293:Adolescent; D044466:Asian People; D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000208:ethnology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human