Sequence analysis of the mitochondrial genome from a large family with maternally inherited nonsyndromic deafness.

Objective To ascertain whether other variations coexist with 1555(A→G) mutation in the mitochondrial DNA and may aggravate the severity of hearing loss or increase the penetrance of 1555(A→G) mutation in a large family with maternally inherited nonsyndromic deafness in Huaiyin, Jiangsu province. Methods PCR-restriction fragment length polymorphism (PCR-RFLP) was used to screen both the nt1555 and the nt7445 of the mitochondrial DNA from 27 maternal members in the core family; and then the mitochondrial genomes from two maternal members, and the 12S rRNA genes MTRNR1 and tRNA-Ser (UCN) gene MTTS1 from the others, were amplified by PCR-RFLP and were sequenced. Results 1555(A→G) mutation in the mitochondrial DNA was reverified to be one of the major factors which cause maternally inherited nonsyndromic deafness and the cosegregation of 955-960(insC) and 1555(A→G) was present in this family. Moreover,7449 (insG), a novel homoplasmic mutation in the tRNA-Ser (UCN) gene, was found to co-exist with 1555(A→G) mutation in two maternal members. Conclusion The cosegregation of 955-960(insC) and 1555(A→G) implies that 955-960(insC) may synergistically cause hearing loss in the presence of an 1555(A→G) mutation,serving as an aggravating factor to enhance the sensitivity to aminoglycosides, and may sometimes increase the penetrance of 1555(A→G) mutation.