Scientists Uncover Genetic Cause For Age-Related hearing Loss

La Jolla, CA (AHN) – A team led by scientists from the Scripps Research Institute has discovered a genetic cause of progressive hearing loss. The new findings will help scientists worldwide gain a better understanding of age-related hearing loss and may lead to new therapies to prevent or treat the condition.

“It is thought that mutations in several hundred genes can lead to deafness,” said team leader Ulrich Mueller, a professor in the Department of Cell Biology and member of the Skaggs Institute for Chemical Biology at Scripps Research. “However, for many forms of deafness, we don’t know what effects the genes have. In this new research, we have linked a previously uncharacterized gene to deafness, first in mice and then in humans.”

The findings published in the latest edition of American Journal of Human Genetics, reveals that the gene responsible for the hearing loss-called Loxhd1-is necessary for maintaining proper functioning hair cells in the inner ear. Mutations in Loxhd1 lead to degradation of the hair cells and a disruption of the process that enables hearing.

In the study, members of the Mueller lab used a technique called forward genetics in their quest to better understand the genetic basis of hearing and hearing loss. The process calls on researchers to make mutations at random in germ cells, screen the resulting models for physical characteristics of interest (in this case hearing impairment), then amplify these traits through the breeding of several generations. The gene responsible for the trait is then identified through positional cloning.

In this case, the scientists were able to generate a new mouse line with hearing impairment that they called samba and then clone the gene responsible, Loxhd1, which had never before been associated with deficits in hearing. When the mice inherited two copies of the mutated gene, they were profoundly deaf shortly after birth.

Researchers conducting the study were then tasked with understanding why this occurred. The scientists found that mutations in the Loxhd1 gene did not appear to affect the initial development of the stereocilia which are critical hair cells for hearing.

However, these mutations did impair the function and maintenance of these essential structures, eventually leading to their degradation and to hearing loss. Even though the study was conducted on mice further analysis on humans found that mutations in the Loxhd1 gene were present in some of these families with hearing loss.

Mueller’s lab is currently investigating the possibility that a therapeutic drug could be effective in reversing the molecular problems that result from the defective gene.