Clinical evaluation and sequence analysis of the complete mitochondrial genome of three Chinese patients with hearing impairment associated with the 12S rRNA T1095C mutation

• DOI: 10.1016/j.bbrc.2004.10.199
• Publication Date: 2004-11-12T17:22:34Z
• Authors: Lidong Zhao; Wie-Yen Young; Roughua Li; Qiuju Wang; Yaping Qian; Min-Xin Guan
• Keywords: Male; 0301 basic medicine; Genome, Human; DNA Mutational Analysis; Sequence Analysis, DNA; Middle Aged; DNA, Mitochondrial; Pedigree; 3. Good health; 03 medical and health sciences; Asian People; RNA, Ribosomal; Humans; Genetic Testing; Child; Hearing Loss

Mutations in mitochondrial DNA (mtDNA), particularly those in the 12S rRNA gene, have been shown to be associated with sensorineural hearing loss. Here we report the clinical and sequence analysis of the entire mitochondrial genome in three Chinese subjects with aminoglycoside-induced and non-syndromic hearing impairment. Clinical evaluation showed a variable phenotype of hearing impairment including the age of onset and audiometric configuration in these subjects. Sequence analysis of the complete mitochondrial genomes in three subjects showed the distinct sets of mtDNA polymorphism, in addition to the identical mitochondrial 12S rRNA T1095C mutation. This mutation was previously identified to be associated with hearing impairment in three families from different genetic backgrounds. The T1095C mutation was absent in 364 Chinese control. In fact, the occurrence of the T1095C mutation in these several genetically unrelated subjects affected by hearing impairment strongly indicates that this mutation is involved in the pathogenesis of hearing impairment. Among other nucleotide changes, the A2238G and T2885C mutations in the 16S rRNA, the I175V mutation in the CO2, the F16L mutation in the A6 and the V112M mutation in the ND6 exhibited a high evolutionary conservation. These data suggest that the T1095C mutation may be associated with aminoglycoside-induced and non-syndromic hearing impairments and A2238G and T2885C mutations in the 16S rRNA, the I175V mutation in the CO2, the F16L mutation in the A6 and the V112M mutation in the ND6 may contribute to the phenotypic expression of the T1095C mutation in these subjects.