A team led by researchers at Cincinnati Children’s has isolated a genetic mutation responsible for deafness associated with Usher syndrome type 1.

Usher syndrome is a genetic defect that causes deafness, night-blindness and a loss of peripheral vision through the progressive degeneration of the retina.  The new findings, published online Sept. 30 in Nature Genetics, eventually could lead to improved treatments for the syndrome.

Researchers conducted genetic analysis of 57 people from Pakistan and Turkey to pinpoint the gene mutation. Their work reveals that the CIB2 protein, which binds to calcium within a cell, is associated with deafness in Usher syndrome type 1 and non-syndromic hearing loss.

“To date, mutations affecting CIB2 are the most common and prevalent genetic cause of non-syndromic hearing loss in Pakistan,” says Zubair Ahmed, PhD, a researcher at Cincinnati Children’s and the study’s lead investigator. “However, we have also found another mutation of the protein that contributes to deafness in Turkish populations.”

In animal models, CIB2 is found in the hair cells of the inner ear, which respond to fluid motion and allow hearing and balance. The protein also is found in retinal photoreceptor cells. The CIB2 mutation appears to interfere with normal calcium signaling that regulates the ear’s ability to convert the mechanical energy of hair cells into electrical signals that the brain can recognize as sound.

“With this knowledge, we are one step closer to understanding the mechanism of mechano-electrical transduction and possibly finding a genetic target to prevent non-syndromic deafness as well as that associated with Usher syndrome type 1,” Ahmed says. 

Saima Riazuddin, PhD, a researcher at Cincinnati Children’s, was co-lead investigator on the study. Other researchers involved in the study include Thomas Friedman, PhD, and Inna Belyantseva, MD, PhD, from the National Institute on Deafness and other Communication Disorders; Suzanne Leal, PhD, and her team at Baylor College of Medicine; and Gregory Frolenkov, PhD, and his team at the University of Kentucky.