Flawed fish jaws shed light on hearing loss in humans

The same genetic tweak that causes malformed jaws in fish could be responsible for some hearing problems in humans, according to USC research in Scientific Reports.

And it all appears to have evolutionary roots.

Scientists believe that the structures that supported the jaws of ancient, ancestral fish gave rise to three tiny bones in the middle ear of humans and other mammals that transmit sound vibrations. The bones are called the malleus, incus and stapes.

A genetic mutation can cause malformation of the jaw in zebrafish, so USC researchers wondered if an equivalent genetic change could trigger hearing defects in mice and humans. To study the question, USC PhD student Camilla Teng brought together colleagues in the USC Stem Cell laboratories of Gage Crump, Rob Maxson and Neil Segil with clinical experts in radiology, audiology and genetics at the Keck School of Medicine of USC and Children’s Hospital Los Angeles.

They studied two genes that are mutated in most patients with Alagille syndrome, a genetic condition that results in various symptoms in different parts of the body, including the liver. In nearly half of patients, the syndrome involves hearing loss in addition to liver, eye heart and skeletal defects. While some of this is hearing loss resulting from deficits in the sensory cells of the inner ear, the researchers also wondered about conductive hearing loss, which involves structural components of the middle ear such as the vibrating bones.

Tests will tell

When the researchers introduced the mutations into mice, they saw defects in both the incus and stapes bones along with corresponding hearing loss.

Later they performed hearing tests on 44 human patients with Alagille syndrome. As predicted by their findings in zebrafish and mice, conductive hearing loss was the most common type, affecting nearly one-third of all ears.

The study sheds light on a mostly overlooked problem problem among people with Alagille syndrome, according to Teng. “If patients are aware of possible conductive hearing loss earlier in life,” she said, “they can more promptly seek medical aids for an improved quality of life.”

Additional co-authors include Hai-Yun Yen, Lindsey Barske, Juan Llamas and John Go from the Keck School of Medicine and Bea Smith and Pedro A. Sanchez-Lara from Children’s Hospital Los Angeles.

Fifty percent of the project was supported by $400,000 of federal funding from the National Institutes of Health (grants/fellowship DE018405, DE024031, DE016320 and DC009975). The other 50 percent of private funding came from the March of Dimes.