Extraction Source: National Institute on Deafness and Other Communication DIsorders(NIDCD), WASHINGTON, DC

Deafness researchers estimate that genetic factors cause 50-60% of severe to profound childhood hearing loss in developed countries. Most DNA is found in the cell nucleus, but DNA can also be found in the mitochondria, the energy-generating structures inside cells. Unlike DNA in the nucleus, which is inherited from both parents, mitochondrial DNA is passed only from mother to child.

Mitochondrial DNA as a Cause of Genetic Hearing Loss

NIDCD scientists have demonstrated that a particular mutation in mitochondrial DNA causes deafness. Their findings are based on a study of a large North American family with maternally inherited deafness and is published in the January 2008 issue of Clinical Genetics.

Earlier studies had identified two large, unrelated families exhibiting many cases of progressive deafness that had been passed to the next generation exclusively by the mother. Both of these families had a rare mutation in a gene, called tRNASer(UCN), located on the mitochondrial DNA. Scientists identified the specific mutation as 7510T>C, but they could not be confident that it was responsible for the families’ deafness.

More recently, NIDCD-supported scientists identified a third large family with hereditary deafness passed to children only by the mother. To explore the genetic cause of this family’s deafness, NIDCD scientists and other National Institutes of Health (NIH) colleagues collaborated with researchers at the Center for Biomedical Research on Rare Diseases in Madrid, and Virginia Commonwealth University in Richmond. The team sequenced the mitochondrial DNA of 5 members of the newly identified North American family, 3 with hearing loss and 2 without. They found 13 variations in the mitochondrial DNA. A total of 12 variations were found in all members of the family and are known to be common changes in mitochondrial DNA (called polymorphisms). One mutation was only found in family members with hearing loss. It was the same 7510T>C mutation as that found in the tRNASer(UCN) gene of the other two families.

To confirm the role of this mutation in causing the hearing loss, scientists analyzed the mitochondrial DNA from 200 unrelated individuals without hearing loss. A total of 78 of these individuals had 11 of the same genetic variations as the North American family and one individual had 12 of the same genetic variations. These shared variations indicated the individuals have the same mitochondrial DNA “fingerprint,” known as a haplogroup—but none of these individuals had the 7510T>C mutation.

The Madrid, Span, research group also studied a Spanish family with maternally inherited deafness and the 7510T>C mutation had a different mitochondrial DNA sequencing. Their results indicated that 7510T>C is not a coincidental variant associated with one particular sequence. The research team concluded that their data “provide strong genetic evidence” that the 7510T>C mutation causes deafness.

Study Conclusions
Although there where variations in the DNA sequences of all four studied families, the common mitochondrial variation in the 7510T>C mutation provides strong evidence that it is this mutation that causes many cases of inherited deafness,