Mitochondrial COI/tRNASer(UCN) G7444A mutation may be associated with hearing impairment in a Han Chinese family

Mutations in mitochondrial genome have been found to be associated with hearing loss. Of these, the mitochondrial 12S rRNA and tRNASer(UCN) are the hot spots for pathogenic mutations associated with deafness. To understand the putative role of mitochondrial DNA (mtDNA) mutations in hearing loss, we recently initiated a mutational screening for the mtDNA mutations in Hangzhou area from Zhejiang Province. In this study, we described a maternally inherited Han Chinese family with high penetrance of hearing loss, notably, the penetrances of hearing loss in this family were 80% and 40%, when the aminoglycoside was included or excluded. Three matrilineal relatives in this pedigree exhibited different levels of hearing loss with different age at onset. In addition, sequence analysis of the complete mitochondrial genome showed the presence of the well-known C1494T mutation in 12S rRNA gene and the G7444A mutation in the COI/tRNASer(UCN). The C1494T mutation had been reported to be a pathogenic mutation associated with aminoglycoside-induced and non-syndromic hearing loss. While the G7444A mutation was considered as a secondary mutation associated with deafness. However, the lack of functional variants in GJB2 and TRMU genes suggested that nuclear modified genes may not play important roles in deafness expression. Thus, the combination of G7444A and C1494T mutations in mitochondrial genome may account for the high penetrance of hearing loss in this Chinese family.