Hearing loss is a very common congenital disorder affecting one in 1000 newborns. More than 50% of deafness cases in the paediatric population have a genetic cause with autosomal dominant, autosomal recessive, X-linked, or mitochondrial patterns of inheritance.¹ Mutations in mitochondrial DNA (mtDNA), particularly in the 12S rRNA and tRNA^Ser(UCN) genes, have been found to be one of the most important causes of sensorineural hearing loss (SNHL).^2,3 The homoplasmic A1555G mutation in the highly conserved decoding site of the mitochondrial 12S rRNA has been found to be associated with both aminoglycoside-induced and non-syndromic SNHL in many families of different ethnic origins.^4–8 Recently, the homoplasmic C1494T mutation in the same gene has also been found to be associated with aminoglycoside-induced and non-syndromic SNHL in a large Chinese family.⁹ In addition, a C-insertion or deletion at position 961 of the 12S rRNA gene has been shown to be associated only with aminoglycoside-induced deafness.^10,11 Furthermore, the mitochondrial tRNA^Ser(UCN) appears to be another hot spot for mutations associated with hearing impairment, as five deafness-associated mutations have been identified in the mitochondrial tRNA^Ser(UCN) gene: A7445G,^12,13 7472insC,¹⁴ T7510C,¹⁵ T7511C,¹⁶ and T7512C.¹⁷ However, non-syndromic deafness-associated mtDNA mutations, such as the A1555G^4–8 or A7445G^12,13 mutation, are often not sufficient to produce the clinical phenotype since some individuals carrying these mutations have normal hearing. Thus, other factors including other mtDNA mutations/polymorphisms and/or nuclear backgrounds or environmental factors modulate the phenotypic variability and penetrance of deafness associated with these mtDNA mutations.