title: [Characterization of two Chinese families with aminoglycoside-induced and nonsyndromic hearing loss both carrying a mitochondrial 12S rRNA 1494C>T mutation].
abstract: OBJECTIVE
  To evaluate the effect of mitochondrial DNA(mtDNA) secondary mutations, haplotypes, GJB2 gene mutations on phenotype of 1494C>T mutation, and to study the molecular pathogenic mechanism of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss.
  
  
  METHODS
  Two Chinese Han pedigrees of maternally transmitted aminoglycoside induced and nonsyndromic hearing loss were collected. The two probands and their family members underwent clinical, genetic and molecular evaluations including audiological examinations and mutational analysis of mitochondrial genome and GJB2 gene.
  
  
  RESULTS
  Clinical evaluation revealed wide range of severity, age-at-onset and audiometric configuration of hearing impairment in matrilineal relatives in both families, for which the penetrance of hearing loss was respectively 42.9% and 28.6% when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss were 14.3% and 14.3%. Sequence analysis of mitochondrial genomes identified a known 12S rRNA 1494C>T mutation, in addition with distinct sets of mtDNA polymorphisms belonging to Eastern Asian haplogroups C4a1a and B4b1c, respectively.
  
  
  CONCLUSIONS
  Mitochondrial 12S rRNA 1494C>T mutation probably underlie the deafness in both families. Lack of significant mutation in the GJB2 gene ruled out involvement of GJB2 in the phenotypic expression. However, aminoglycosides and other nuclear modifier genes may still modify the phenotype of the 1494C>T mutation in these families. The B4b1c is a newly identified haplogroup in aminoglycoside-induced and nonsyndromic hearing loss family carrying the 1494C>T mutation. The 1494C>T mutation seems to have occurred sporadically through evolution.
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Sha-sha
authors.initials: SS
authors.lastname: Gong
authors.forename: Bo-bei
authors.initials: BB
authors.lastname: Chen
authors.forename: Guang-hua
authors.initials: GH
authors.lastname: Peng
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Bin-jiao
authors.initials: BJ
authors.lastname: Zheng
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Chu-qin
authors.initials: CQ
authors.lastname: Zhang
authors.forename: Jian-xin
authors.initials: JX
authors.lastname: Lv
authors.forename: Min-xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000328:Adult; D000617:Aminoglycosides / Q000009:adverse effects; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D034381:Hearing Loss / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012335:RNA, Ribosomal / Q000235:genetics*; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D017630:Connexins; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D000072259:Connexin 26