Mutations in
mitochondrial DNA (
mtDNA), especially in mitochondrial
12S rRNA and
transfer RNA(
tRNA)Ser(UCN) genes, are important causes of non‑syndromic
hearing loss. However, the molecular mechanism underlying mt‑tRNA mutations in clinical
hearing impairment are not fully understood. The present study assessed the molecular characterization of two Chinese families with non‑syndromic
hearing loss, who both exhibited very low penetrance of
deafness (9.1 and 12.5% for Family 1 and 2, respectively). Mutational analysis of the complete
mtDNA genes identified the presence of cytochrome c
oxidase 1/
tRNASer(UCN) G7444A and
tRNASer(UCN) C7492T mutations, together with polymorphisms belonging to human mitochondrial haplogroup D4 and G2b, respectively. Moreover, the G7444A and C7492T mutations occurred at highly conserved
tRNASer(UCN)
nucleotides and may cause
tRNA metabolism failure, which is involved in mitochondrial translation defects. Therefore, the G7444A and C7492T mutations may lead to the
mitochondrial dysfunction that responsible for
deafness. However, the absence of any functional variants in Gap junction β‑2, Solute Carrier Family 26 Member 4 and
TRNA 5‑methylaminomethyl‑2‑thiouridylate
methyltransferase suggested that nuclear genes may not play active roles in the occurrence of
deafness. In the present study, the observed incomplete penetrance of
hearing loss and mild
mitochondrial dysfunction indicated that
mtDNA G7444A and C7492T mutations are insufficient to produce the
deafness phenotype. Therefore, other risk factors such as environmental factors and epigenetic regulation may be involved in the pathogenesis of
hearing loss in the families recruited in the present study.