Unique penetrance of hearing loss in a five-generation Chinese family with the mitochondrial 12S rRNA 1555A > G mutation.

CONCLUSIONS

Analysis of the complete mtDNA genome and X-linkage of this five-generation Chinese family revealed that the 1555A > G mutation may lead to deafness.

OBJECTIVES

Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. However, the variable clinical phenotype and incomplete penetrance of mtDNA 1555A > G-induced hearing loss complicate our understanding of this mutation. We aimed to identify whether nuclear genes, mitochondrial haplotypes/variants, and a possible threshold effect are involved in its manifestation in the pedigree.

METHODS

We performed clinical, genetic, and X-linkage analysis of a five-generation Chinese family in which all the affected individuals were male.

RESULTS

Clinical evaluation revealed that affected individuals with or without aminoglycoside exposure developed hearing loss extending gradually from 8000 Hz to 4000 Hz and then to 1000 Hz. Using X-linkage analysis and sequencing, we detected an identical homoplasmic 1555A > G mutation in nine individuals, and a previously unreported variant 14163C > T in mtDNA. The new variant 14163C > T coexisted with the 1555A > G mutation in six affected subjects of our pedigree. The previously unreported variant 14163C > T and aminoglycoside exposure may synergize the development of this deafness.