title: [A novel mutation T8821G in mitochondrial DNA may be associated with Leber's hereditary optic neuropathy].
abstract: OBJECTIVE
  To report on clinical, genetic and molecular characterization of two Chinese families with Leber's hereditary optic neuropathy.
  
  
  METHODS
  Ophthalmological examinations have revealed variable severity and age at onset of visual loss among the probands and other matrilineal relatives of both families. The entire mitochondrial genome of the two probands was amplified with PCR in 24 overlapping fragments using sets of oligonucleotide primers.
  
  
  RESULTS
  The ophthalmological examinations showed that penetrance was 12.5% and 30.0% respectively in the two families. Sequence analysis of the complete mitochondrial genomes in these pedigrees has identified unreported homoplasmic T8821G mutation in the ATPase 6 gene and distinct sets of polymorphisms belonging to haplogroups M10a. The T8821G mutation has occurred at the extremely conserved nucleotide (conventional position 99) of the ATPase6. Thus, this mutation may alter structural formation of ATPase6, thereby leading to failure in the synthesis of ATP involved in visual impairment.
  
  
  CONCLUSIONS
  Above observations have suggested that the ATPase6 T8821G mutation may be involved in the pathogenesis of optic neuropathy in these families.
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Wenzhou, Zhejiang 325035, P. R. China.gminxin88@zju.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Sai
authors.initials: S
authors.lastname: Zhang
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Fuxin
authors.initials: F
authors.lastname: Zhao
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.forename: Qiping
authors.initials: Q
authors.lastname: Wei
authors.forename: Yi
authors.initials: Y
authors.lastname: Tong
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.forename: Minxin
authors.initials: M
authors.lastname: Guan
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D008969:Molecular Sequence Data; D029242:Optic Atrophy, Hereditary, Leber / Q000201:enzymology* / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; C501005:MT-ATP6 protein, human; D025261:Mitochondrial Proton-Translocating ATPases