Gene Linked to a Form of Progressive Hearing Loss is Identified
A gene associated with a form of inherited progressive hearing loss has been identified by an international team of researchers, led in part by Xue Zhong Liu, M.D., Ph.D., associate professor of otolaryngology at the Miller School. The gene, SMAC/DIABLO, appears to be crucial in inner ear development and maintenance. The findings were published online on July 1 in The American Journal of Human Genetics.
The researchers identified the gene which is associated with the deafness locus DFNA64. The researchers used linkage and positional candidate gene screening in six generations of one Chinese family with dominant progressive non-syndromic hearing loss with over 50 affected individuals. Individuals with DFNA64 begin to lose hearing in both ears roughly between the ages of 12 and 30, and over the course of several decades will experience hearing loss that can range from moderate to severe.
The SMAC/DIABLO gene encodes a mitochondria proapoptotic protein, which is released from the mitochondria during apoptosis and counters the inhibitory activities of inhibitors of apoptosis proteins, and appears to play a key role in inner ear development and maintenance. The mutation identified in the SMAC/DIABLO gene, which is a decrease in the production of the Diablo protein, results in mitochondria dysfunction, which eventually leads to progressive hearing loss.
“DFNA64 is the first example of a human disease caused by a mutation in the SMAC/DIABLO gene,” said Thomas Van de Water, Ph.D., research professor of otolaryngology and director of the Cochlear Implantation Center at the University of Miami Ear Institute. “The findings emphasize the importance of a genetic approach for uncovering hearing impairment caused by apoptosis.”
The knowledge that scientists gather about the mechanisms of SMAC/DIABLO could potentially be used to develop treatments to combat progressive hearing loss.
Hui Jun Yuan, M.D., Ph.D., of Chinese PLA General Hospital (301), Beijing, and Zheng-Yi Chen D.Phil, of Harvard Medical School, also headed up the research team with Dr. Liu.
