Hearing loss may be associated with the novel mitochondrial tRNA(Asp) A7551G mutation in a Chinese family / 中华耳鼻咽喉头颈外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>We reported here the clinical and genetic evaluations as well as mutational analysis of mitochondrial DNA(mtDNA) in a Chinese family with maternally transmitted non-syndromic hearing loss and investigated the influence of the mitochondrial tRNA(Asp) A7551G mutation to the phenotypic manifestation of the deafness.</p><p><b>METHODS</b>One Chinese Han pedigrees of maternally transmitted nonsyndromic hearing loss were collected. The proband and family members underwent clinical, genetic, and molecular evaluations, such as audiological examinations, mutational analysis of mitochondrial genome and mutational analysis of GJB2 gene.</p><p><b>RESULTS</b>Six people of this pedigree suffered from hearing loss, including four matrilineal members, and others did not have significant clinical abnormalities. Sequence analysis of the complete mitochondrial genome in the proband showed that there were 28 mtDNA polymorphisms belonging to East -Asian haplogroup A4.In addition to the A7551G homogeneity mutation, there were no other functionally significant variants found in this family. The A7551G mutation located immediately at the three prime end to the anticodon, corresponding with the conventional position 37 of tRNA(Asp), and its' CI value was 100% compared with other 15 primate species. The A7551G mutation was absent in other Chinese controls. The mutations on GJB2 were detected by direct sequence analysis,GJB2 235delC and 299delAT which was associated with hearing loss were found in the genomic DNA of the proband and some matrilineal members. Clinical evaluation showed a variable phenotype of severity, age-at-onset and audiometric configuration of hearing loss in the matrilineal relatives in these families.</p><p><b>CONCLUSIONS</b>The A7551G mutation may modify the secondary structure of the tRNA, and affect the stabilization of tRNA(Asp), produce non-normal functional tRNA(Asp) ultimately. And it may cause the phenotypic manifestation of the deafness that associated with A7551G mutation. Therefore, the mitochondrial tRNA(Asp) A7551G mutation may be a new mitochondrial mutation for hearing loss.</p>