title: [Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss in five Han Chinese pedigrees].
abstract: OBJECTIVE
  To study the effect of the mitochondrial 12S rRNA mutations on aminoglycoside-induced and nonsyndromic hearing loss, to carry out the clinical and molecular characterization of five Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss.
  
  
  METHODS
  Five pedigrees of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss were collected, genomic DNA was extracted, and complete mitochondrial genomes and the gap junction protein beta 2 (GJB2) gene were amplified and sequenced.
  
  
  RESULTS
  Clinical evaluation revealed a wide range of severity, age-at-onset and audiometric configuration of hearing impairment in the matrilineal relatives in these families. The penetrance rates of hearing loss in these pedigrees were 17.6%, 50.0%, 66.7%, 31.3% and 23.1%, with an average of 37.7%, when aminoglycoside-induced deafness was included. Sequence analysis of the complete mitochondrial genomes in these pedigrees identified the known 1555A>G mutation and distinct sets of mitochondrial DNA(mtDNA) polymorphisms belonging to Eastern Asian haplogroups D4b2b, B4c1b1, F3, C1 and D5a, respectively. Of these variants, ND1 L89T and CO3 A200T mutations resided at the highly conservative regions. However, there were no functionally significant mutations in tRNAs and rRNAs or secondary known mutations. No hearing loss related GJB2 gene mutation was observed.
  
  
  CONCLUSIONS
  The lack of significant mutation in the ruled out the possible involvement of GJB2 in the phenotypic expression of the 1555A>G mutation in those affected subjects. However, aminoglycosides, mtDNA variations and other nuclear modifier genes may play an important role in the phenotypic manifestation of the 1555A>G mutation in these Chinese families.
authors.affiliation: Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Wenzhou, Zhejiang 325035, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Bo-bei
authors.initials: BB
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Sha-sha
authors.initials: SS
authors.lastname: Gong
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; D000595:Amino Acid Sequence; D000617:Aminoglycosides / Q000009:adverse effects*; D000818:Animals; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China / Q000208:ethnology; D000072259:Connexin 26; D017630:Connexins / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009035:Mothers; D010375:Pedigree; D055815:Young Adult
chemical_list: D000617:Aminoglycosides; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26