Miller School Researchers Help Discover Gene Linked to Hearing Loss

Investigators from around the world, including the University of Miami Miller School of Medicine, have discovered a gene linked to a type of hearing loss called auditory neuropathy spectrum disorder.

Their discovery, described in a paper published in the Proceedings of the National Academy of Sciences, could lead to new treatments for age-related progressive hearing loss, according to study author Xue Zhong Liu, M.D., Ph.D., FACS, Marian and Walter Hotchkiss Endowed Chair in Otolaryngology and vice chair of otolaryngology at the Miller School.

Dr. Xue Zhong Liu

Hearing loss is the most common human sensory deficit, impacting 15% to 26% of the world’s population.

“There is a great deal that is still unknown about what causes hearing loss, especially in aging populations. We know of more than 100 genes that are linked to hearing loss, but they can explain only about one-third of cases,” Dr. Liu said.

Miller School investigators worked with scientists at other institutions, including Harvard Medical School, to find that a mutation in the transmembrane protein 43 (TMEM43) gene is linked to hearing loss in humans and mice.

People with auditory neuropathy spectrum disorder respond to sound but have difficulty deciphering speech.

Dr. Liu and colleagues studied two Asian families with hereditary late-onset auditory neuropathy spectrum disorder with progressive hearing loss. They identified a link between an abnormality in the cochlear glia-like supporting cells and impaired speech discrimination.

“Based on the pathology mainly involving cochlear glial cells, we performed cochlear implant procedures on the patients and their speech discrimination ability was restored,” Dr. Liu said. “So, we have not only found a new genetic cause of deafness. This study also unveils a gene playing a fundamental role in hearing and speech discrimination in specific ear cells in different species, which has opened new frontiers for the development of effective treatments for hearing loss. Our findings also will inform future research on therapeutic targets.”

The paper goes a step further, providing a model platform that can determine the personalized timing and mode of auditory rehabilitation, highlighting the importance of a precision medicine-based approach.

“There is no cure for hearing loss,” Dr. Liu said. “Current therapies for hearing loss range from sound amplification to cochlear implantation. These interventions have significant limitations and clearly do not restore hearing to normal levels.”

Genes for progressive hearing loss are good candidates for gene- and cell-based therapies since patients with mutations typically have progressive rather than profound congenital hearing loss. As a result, there is a longer window of opportunity for interventions, Dr. Liu said.

Other Miller School authors on the paper are Susan Halloran Blanton, Ph.D., professor in the Dr. John T. Macdonald Foundation Department of Human Genetics and the Department of Otolaryngology; Aida Nourbakhsh, M.D., Ph.D., otolaryngology resident; and Zaohua Huang, Ph.D., associate scientist.

Tags: auditory neuropathy spectrum disorder, Department of Otolaryngology, Dr. Xue Zhong Liu, Proceedings of the National Academy of Sciences