title: The clinical and audiologic features of hearing loss due to mitochondrial mutations.
abstract: OBJECTIVE
  To characterize mitochondrial sequence variants present in a nationwide hereditary deafness DNA repository of samples from deaf subjects and to define the clinical presentation and audiometric characteristics of individuals with a mitochondrial sequence variant.
  
  
  METHODS
  Retrospective review of results for select mitochondrial mutations performed on DNA samples from subjects compiled from 1997 to 2009.
  
  
  METHODS
  National hereditary deafness DNA repository.
  
  
  METHODS
  Available samples from subjects in the repository were screened to identify those with mitochondrial sequence variants. Clinical data on the nature of mutation, type and severity of the hearing loss, and sex, age at diagnosis, family history of hearing loss, and ethnicity were analyzed.
  
  
  RESULTS
  Eighty-six patients were identified with mitochondrial mutations or 3.5% of the subjects studied. Among those with mitochondrial mutations, 21 (24.4%) had the m.7445A>G substitution, 18 (20.9%) had the m.1555A>G substitution, 18 (20.9%) had the m.961T>G substitution, and 29 (33.7%) had a m.961delT+C(n) complex deletion. The majority of patients had bilateral severe to profound hearing loss. Fifty-three (62%) patients were female, and a family history of hearing loss was documented in 66 (76.7%) patients. The deafness was recognized prior to 3 years of age in 26 patients.
  
  
  CONCLUSIONS
  Mitochondrial deafness in this sample was associated with a variety of genetic mutations and a wide spectrum of clinical presentations. Because of increased aminoglycoside susceptibility associated with some forms of mitochondrial deafness, matrilineal relatives may be at risk in those cases, highlighting the importance of making an accurate diagnosis prior to exposure.
authors.affiliation: Virginia Commonwealth University Health Systems, Department of Otolaryngology-Head and Neck Surgery, 1200 East Broad St, West Hospital, Richmond, Virginia 23298-0146, USA. joshua.yelverton@gmail.com
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Yelverton
authors.forename: Kathleen
authors.initials: K
authors.lastname: Arnos
authors.forename: Xia-Juan
authors.initials: XJ
authors.lastname: Xia
authors.forename: Walter E
authors.initials: WE
authors.lastname: Nance
authors.forename: Arti
authors.initials: A
authors.lastname: Pandya
authors.forename: Kelley M
authors.initials: KM
authors.lastname: Dodson
mesh_terms: D000328:Adult; D017677:Age Distribution; D001299:Audiometry / Q000379:methods; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D016208:Databases, Factual; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D034381:Hearing Loss / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012189:Retrospective Studies; D017678:Sex Distribution; D014481:United States
chemical_list: D004272:DNA, Mitochondrial
keywords: DNA mutations; aminoglycoside; deafness; matrilineal inheritance; mitochondria; nonsyndromic hearing loss