Scientists discovered mutations in a gene that lead to hearing loss and also contribute to Usher syndrome. The finding adds to a growing body of knowledge about the biological pathways involved in these disorders. Usher syndrome is a hereditary disease in an autosomal recessive pattern, which affected individuals lose both hearing and vision. There are 3 clinical types of Usher syndrome. In the United States, types 1 and 2 are the most prevalent.
There are many syndromes that affect both the visual and auditory systems but Usher syndrome is the most common genetic cause of deafness and blindness among school age children. Mutations in different genes are currently ascribed as the cause of Usher syndrome.
Several genes associated with different types of Usher syndrome have been identified. Most of these genes encode common structural and motor proteins that build sensory cells in the eye and inner ear.
In the new study researchers found that the mutations responsible were in a gene called CIB2. Zubair M.
- Ahmed, Saima Riazuddin, Thomas B. Friedman and their teams have identified this gene on chromosome 15 and determined that its mutations are responsible for nonsyndromic deafness and Usher syndrome type I. CIB2 was found to be interacting with other proteins associated with Usher syndrome.
- Mutations in a gene called CIB2, which provides the genetic code for a protein that binds both calcium and integrin, is associated with deafness—both in a disorder called Usher syndrome and in deafness that does not result from a syndrome, said an international group of researchers.
“These mutations are among the major causes of hearing impairment in many of the families studied in Pakistani population. The scientists also linked a mutation in the gene with deafness in a Turkish family”.
CIB2 belongs to a family of proteins that bind calcium and integrins, a type of protein that is thought to regulate calcium concentration in specific places inside the cell. Experiments revealed that the newly identified mutations affect the way CIB2 binds calcium.
The proteins these genes produce are thought to interact to influence the structure and function of stereocilia, bristly structures that sit atop sensory “hair” cells in the inner ear. Future studies may target CIB2 to influence the progression and severity of Usher syndrome.
- Suzanne Leal and her team at the Baylor College of Medicine found that in Pakistan, CIB2 mutations are one of the prevalent genetic causes of nonsyndromic hearing loss.
- Inna Belyantseva at the National Institute on Deafness and Other Communication Disorders, the National Institutes of Health, established that CIB2 is localized at the tips of mechanosensory stereocilia of the inner ear hair cells, exactly where the conversion of sound waves into electrical signals occurs.
- Frolenkov and his team at UK demonstrated that disease-associated mutations in CIB2 change the ability of this protein to bind intracellular calcium; in a zebra fish model, its loss disrupts mechanosensitivity in the hair cells.
- Tiffany Cook, Elke Buschback and their team at University of Cincinnati knockdown CIB2 analog in Drosophila (fruit fly) eyes and observed calcium-dependent degeneration of photoreceptors and loss of sensitivity to repetitive light pulses.
All these data suggest that CIB2 is a common protein influencing intracellular calcium responses during conversion of light and sound into electrical signals. The researchers hypothesized that CIB2 plays a role in mechanotransduction the process by which sound waves are transformed into the electrical signals that the brain recognizes as sound. CIB2 joins now a growing list of genes associated with Usher syndrome.
“With this knowledge, we are one step closer to understanding the mechanism of mechano-electrical transduction,” says one of the researchers.