Early-Onset Sensorineural Hearing Loss and Late-Onset Neurologic Complaints Caused by a Mitochondrial Mutation at Position 7472 | Genetics and Genomics | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Pavlakis  SGPhillips  PCDimauro  SDe Vivo  DCRowland  LP Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome.  Ann Neurol. 1984;16481- 488Google ScholarCrossref
Shoffner  JMLott  MTLezza  AMSSeibel  PBallinger  SWWallace  DC Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNAtRNAlys mutation.  Cell. 1990;61931- 937Google ScholarCrossref
Degoul  FNelson  ILestienne  P  et al.  Deletions of mitochondrial DNA in Kearns Sayre and ocular myopathy: genetic, biochemical and morphological studies.  J Neurol Sci. 1991;101168- 177Google ScholarCrossref
DiMauro  SBonilla  EZeviani  MNakagawa  MDe Vivo  DC Mitochondrial myopathies.  Ann Neurol. 1985;17521- 538Google ScholarCrossref
Gold  MRapin  I Non-Mendelian mitochondrial inheritance as a cause of progressive sensorineural hearing loss.  Int J Pediatr Otorhinolaryngol. 1994;3091- 104Google ScholarCrossref
Zeviani  MBresolin  NGellera  C  et al.  Nucleus-driven multiple large scale deletions of the mitochondrial genome: a new autosomal dominant disease.  Am J Hum Genet. 1990;47904- 914Google Scholar
Cormier  PRötig  ATardieu  MColonna  MSaudubray  JMMunnich  A Autosomal dominant deletions of mitochondrial genome in a case of progressive encephalomyopathy.  Am J Hum Genet. 1991;48643- 648Google Scholar
Van den Ouweland  JMLemkes  HHPRuitenbeek  W  et al.  Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness.  Nat Genet. 1992;1368- 371Google ScholarCrossref
Tiranti  VChariot  PCarella  F  et al.  Maternally inherited hearing loss, ataxia and myoclonus associated with a novel point mutation in mitochondrial tRNA-ser (UCN) gene.  Hum Mol Genet. 1995;41421- 1427Google ScholarCrossref
Vernham  GAReid  FMRundle  PAJacobs  HT Bilateral sensorineural hearing loss in members of a maternal lineage with a mitochondrial point mutation.  Clin Otolaryngol. 1994;19314- 319Google ScholarCrossref
Fischel-Ghodsian  NPrezant  TRFournier  PStewart  IAMaw  M Mitochondrial mutation associated with non-syndromic deafness.  Am J Otolaryngol. 1995;16403- 406Google ScholarCrossref
Jaber  LShohat  MBo  X  et al.  Sensorineural deafness inherited as a tissue specific mitochondrial defect.  J Med Genet. 1992;2986- 90Google ScholarCrossref
Prezant  TRAgapian  JVBohlman  C  et al.  Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.  Nat Genet. 1993;4289- 294Google ScholarCrossref
Hu  DQiv  WQWu  BT  et al.  Genetic aspects of antibiotic induced deafness: mitochondrial inheritance.  J Med Genet. 1991;2879- 83Google ScholarCrossref
International Organization for Standardization, ISO 8253-1: Acoustics: Audiometric Test Methods, I: Basic Pure Tone Air and Bone Conduction Threshold Audiometry.  Geneva, Switzerland International Organization for Standardization1989;
International Organization for Standardization, ISO 7029: Acoustics: Threshold of Hearing by Air Conduction as a Function of Age and Sex for Otologically Normal Persons.  Geneva, Switzerland International Organization for Standardization1984;
Huygen  PLM Nystagmometry: the art of measuring nystagmus parameters by digital signal processing.  ORL J Otorhinolaryngol Relat Spec. 1979;41206- 220Google ScholarCrossref
Huygen  PLM Vestibular hyperreactivity in patients with multiple sclerosis.  Adv Otorhinolaryngol. 1993;30141- 149Google Scholar
Fischer  JCRuitenbeek  WGabreels  FJM A mitochondrial encephalomyopathy: the first case with an established defect at the level of co-enzyme Q.  Eur J Pediatr. 1986;144441- 444Google ScholarCrossref
Elverland  HHTorbergsen  T Audiological findings in a family with mitochondrial disorder.  Am J Otol. 1991;6459- 465Google Scholar
Swift  ACSingh  SD Hearing impairment and the Kearns-Sayre syndrome.  J Laryngol Otol. 1988;102626- 627Google ScholarCrossref
Donovan  TJ Mitochondrial encephalomyopathy: a rare genetic cause of sensorineural hearing loss.  Ann Otol Rhinol Laryngol. 1995;104786- 792Google Scholar
Schutta  HSJohnson  L Encephalopathy in the Gunn rat: a fine structure of the cerebellar cortex.  J Neuropathol Exp Neurol. 1967;26377- 396Google ScholarCrossref
Suomalainen  AMajander  AHaltia  M  et al.  Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia.  J Clin Invest. 1992;9061- 66Google ScholarCrossref
Jackson  MJSchaefer  JAJohnson  MAMorris  AAMTurnbull  DMBindoff  LA Presentation and clinical investigation of mitochondrial respiratory chain disease: a study of 51 patients.  Brain. 1995;118339- 357Google ScholarCrossref
Original Article
August 1998

Early-Onset Sensorineural Hearing Loss and Late-Onset Neurologic Complaints Caused by a Mitochondrial Mutation at Position 7472

Author Affiliations

From the Departments of Otorhinolaryngology (Drs Ensink, Marres, Huygen, and Cremers) and Neurology (Drs Padberg and ter Laak), University Hospital Nijmegen, Nijmegen, the Netherlands; and the Department of Medical Genetics, University of Antwerp, Antwerp, Belgium (Drs van Camp and Willems, and Ms Verhoeven).

Arch Otolaryngol Head Neck Surg. 1998;124(8):886-891. doi:10.1001/archotol.124.8.886

Objectives  To detect a mitochondrial mutation responsible for maternally transmitted hearing loss with late-onset neurologic features in a 3-generation Dutch family, and to describe the hearing loss, associated symptoms, and vestibular dysfunction.

Patients and Methods  All maternally related family members (n=69) were investigated using standard audiometry. In a selected group, vestibulo-ocular examinations and additional neurologic and ophthalmologic examinations were performed. Twenty milliliters of venous blood was taken from all participants for genetic studies.

Setting  University medical center.

Results  All maternally related individuals carried an extra C at position 7472 of the mitochondrial genome. Hearing loss was the only symptom or presenting symptom in most family members and most pronounced at higher frequencies. Hearing loss at lower frequencies was demonstrated in individuals 10 years and older. Most patients had vestibular hyperreactivity and were susceptible to motion sickness, suggesting vestibulocerebellar dysfunction. Neurologic complaints were infrequent and presented by older individuals; however, numerous enlarged mitochondria were found in a muscle biopsy specimen of an individual with hearing impairment but without neurologic symptoms.

Conclusions  Respiratory chain dysfunction should be considered as a possible cause of progressive sensorineural hearing loss. More research into the causes of high-frequency impairment should be considered, especially when sensorineural hearing loss, syndromal or nonsyndromal, is exclusively maternally transmitted. Maternal transmission of hearing impairment can also be valuable in the diagnosis of unclear neurologic syndromes.