title: Sequence analysis of the mitochondrial genome from a large family with maternally inherited nonsyndromic deafness.
abstract: OBJECTIVE
  To ascertain whether other variations coexist with 1555(A--> G) mutation in the mitochondrial DNA and may aggravate the severity of hearing loss or increase the penetrance of 1555(A--> G) mutation in a large family with maternally inherited nonsyndromic deafness in Huaiyin, Jiangsu province.
  
  
  METHODS
  PCR-restriction fragment length polymorphism (PCR-RFLP) was used to screen both the nt1555 and the nt7445 of the mitochondrial DNA from 27 maternal members in the core family; and then the mitochondrial genomes from two maternal members, and the 12S rRNA genes MTRNR1 and tRNA-Ser(UCN) gene MTTS1 from the others, were amplified by PCR-RFLP and were sequenced.
  
  
  RESULTS
  1555(A--> G) mutation in the mitochondrial DNA was reverified to be one of the major factors which cause maternally inherited nonsyndromic deafness and the cosegregation of 955-960(insC) and 1555(A--> G) was present in this family. Moreover, 7449 (insG), a novel homoplasmic mutation in the tRNA-Ser(UCN) gene, was found to co-exist with 1555(A--> G) mutation in two maternal members.
  
  
  CONCLUSIONS
  The cosegregation of 955-960(insC) and 1555(A--> G) implies that 955-960(insC) may synergistically cause hearing loss in the presence of an 1555(A--> G) mutation, serving as an aggravating factor to enhance the sensitivity to aminoglycosides, and may sometimes increase the penetrance of 1555(A--> G) mutation.
authors.affiliation: Genetics Research Center, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009 PR China.
authors.forename: Hai-jun
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Chun-hong
authors.initials: CH
authors.lastname: Xu
authors.forename: Yi-ju
authors.initials: YJ
authors.lastname: Zhan
authors.forename: Su-ying
authors.initials: SY
authors.lastname: Zhao
authors.forename: Yun-feng
authors.initials: YF
authors.lastname: Shan
authors.forename: Xue-xia
authors.initials: XX
authors.lastname: Geng
authors.forename: Xiang-nian
authors.initials: XN
authors.lastname: Shan
mesh_terms: D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D054629:Genome, Mitochondrial / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial