title: [The mitochondrial tRNA(Thr) A15951G mutation may be associated with Leber's hereditary optic neuropathy in two Chinese families].
abstract: OBJECTIVE
  To explore clinical, genetic and molecular features of two Chinese Han families with Leber's hereditary optic neuropathy (LHON).
  
  
  METHODS
  Ophthalmologic examinations revealed variable severity and age-at-onset of visual loss among probands and other matrilineal relatives of both families. The families exhibited extremely low penetrance of visual impairment. The entire mitochondrial genome of two probands was amplified by PCR in 24 overlapping fragments using sets of oligonucleotide primers.
  
  
  RESULTS
  Sequence analysis of complete mitochondrial genome in the pedigrees excluded three common LHON associated mutations G11778A, G3460A and T14484C, but revealed the presence of a known homoplasmic tRNA(Thr) A15951G mutation. It also showed distinct sets of mtDNA polymorphisms belonging to Eastern Asian haplogroup D4b1. The A15951G mutation is located at the extremely conserved nucleotide (conventional position 71) of tRNA(Thr). Thus, this mutation may alter the structure and stability of mitochondrial tRNA(Thr), thereby leading to a failure in the tRNA metabolism and mitochondrial dysfunction, causing visual impairment.
  
  
  CONCLUSIONS
  The results suggested that the A15951G mutation might be involved in the pathogenesis of Leber's hereditary optic neuropathy in the two families.
authors: Giuseppe Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, Zhejiang, People's Republic of China.
authors: Yu
authors: Y
authors: Zhang
authors: Juan-juan
authors: JJ
authors: Zhang
authors: Yan-chun
authors: YC
authors: Ji
authors: Ming-lian
authors: ML
authors: Zhang
authors: Yi
authors: Y
authors: Tong
authors: Fu-xin
authors: FX
authors: Zhao
authors: Jia
authors: J
authors: Qu
authors: Xiang-tian
authors: XT
authors: Zhou
authors: Min-xin
authors: MX
authors: Guan
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D012363:RNA, Transfer, Thr / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D012363:RNA, Transfer, Thr