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Keywords:

  • deafness;
  • mitochondrial DNA;
  • nonsyndromic hearing impairment

Mitochondria are intracellular organelles responsible for the majority of a cell's energy production. They have their own small maternally inherited genome which, when mutated, can give rise to a large spectrum of diseases. The phenotype most commonly includes neurological and muscular symptoms, although hearing impairment is an additional feature in some mitochondrial syndromes. Often, syndromic mutations affect only a fraction of all mitochondrial DNA molecules, a condition referred to as heteroplasmy. It is believed that the degree of heteroplasmy in different tissues contributes to the phenotypic heterogeneity that is a hallmark of these syndromes. Five homoplasmic mutations leading to nonsyndromic hearing impairment have been reported (1555A[RIGHTWARDS ARROW]G, 7445A[RIGHTWARDS ARROW]G, 7472insC, 7510T[RIGHTWARDS ARROW]C, 7511T[RIGHTWARDS ARROW]C). The 1555A[RIGHTWARDS ARROW]G is in the 12S rRNA gene, and in some populations, appears to be a frequent cause of hearing impairment. Carriers of the mutation are abnormally sensitive to aminoglycoside-induced ototoxicity even at ‘appropriate’ drug levels; in addition, even without aminoglycoside exposure, these persons can develop hearing impairment. The other four nonsyndromic mutations are located in the tRNASer(UCN) gene. In addition to hearing impairment, with two of these mutations (7445A[RIGHTWARDS ARROW]G, 7472insC), other symptoms can be present. In some patients, however, why these five mutations preferentially affect the inner ear, despite the crucial role of mitochondria in nearly all cells of the body, is unknown.