Molecular Pathogenetic Mechanism of Maternally Inherited Deafness

Authors

  • MIN-XIN GUAN

    Corresponding author
    1. Division and Program in Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
      Address for correspondence: Min-Xin Guan, Ph.D., Division and Program in Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039. Voice: 513-636-3337; fax: 513-636-3486. min-xin.guan@chmcc.org
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Address for correspondence: Min-Xin Guan, Ph.D., Division and Program in Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039. Voice: 513-636-3337; fax: 513-636-3486. min-xin.guan@chmcc.org

Abstract

Abstract: Mutations in the mitochondrial DNA (mtDNA) have been shown to be one important cause of deafness. In particular, mutations in the mtDNA have been associated with both syndromic and nonsyndromic forms of sensori-neural hearing loss. The deafness-linked mutations often occur in the mitochondrial 12S rRNA gene and in tRNA genes. Mutations in the 12S rRNA gene account for most of the cases of aminoglycoside ototoxicity. The other hot spot for mutations associated with hearing impairment is the tRNASer(UCN) gene, as five deafness-linked mutations have been identified in this gene. Nonsyndromic deafness-linked mtDNA mutations are often homoplasmic or at high levels of heteroplasmy, indicating a high threshold for pathogenicity. Phenotypic expression of these mtDNA mutations requires the contribution of other factors such as nuclear modifier gene(s), environmental factor(s), or mitochondrial haplotype(s).

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