Sequence analysis of the mitochondrial genome from a large family with maternally inherited nonsyndromic deafness / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>