OBJECTIVETo investigate the relationship of mitochondrial DNA mutations with inherited deafness in a maternally inherited pedigree with non-syndromic deafness.

METHODSThe diagnosis was validated by hearing tests. Blood samples were collected from 18 maternal members of the family and 53 controls including 6 paternal members, 7 spouses and 40 unrelated individuals. DNA was extracted from the leukocytes in blood samples. The gene fragments of mitochondrial DNA 12S rRNA, tRNA(Ser(UCN)) and GJB2 gene were amplified by polymerase chain reaction(PCR). PCR products were analyzed by sequencing. Computerized 12S rRNA secondary structure modeling was carried out to characterize the mutation found in the family.

RESULTSA novel mitochondrial DNA 12S rRNA 709 G to A transition was detected from all maternal members including 8 patients with hearing loss and other 10 symptom-free maternal members. Non-maternal members and other controls did not carry this mutation. In addition, the tRNA(Ser(UCN))A7445G, 12S rRNA A1555G and GJB2 gene mutations were not observed in the study. Computerized modeling showed that this mutation changed the eighth and ninth loop-stem structure of the 12S rRNA secondary structure.

CONCLUSIONIn this family, 8 deaf patients carried the mitochondrial DNA 12S rRNA 709 G to A mutation, which is highly conservative in healthy adults. It was confirmed that the mitochondrial DNA 12S rRNA gene G709A was associated with non-syndromic inherited hearing loss. The other 10 maternal members carried the mutation, but they did not suffer from deafness, which might suggest that the G709A mutation may cause hearing impairment in combination with a synergistic effect of some other nuclear modifier genes.